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Colin S Duckett

Professor of Pathology
Pathology
Dean's Suite, Room 128, Davison Building, Durham, NC 27710
Dean's Suite, Rm 128, Davison Building, Durham, NC 27710

Selected Publications


Molecular mechanisms of cell death: recommendations of the Nomenclature Committee on Cell Death 2018.

Journal Article Cell Death Differ · March 2018 Over the past decade, the Nomenclature Committee on Cell Death (NCCD) has formulated guidelines for the definition and interpretation of cell death from morphological, biochemical, and functional perspectives. Since the field continues to expand and novel ... Full text Open Access Link to item Cite

Heat Shock Protein 70 (Hsp70) Suppresses RIP1-Dependent Apoptotic and Necroptotic Cascades.

Journal Article Mol Cancer Res · January 2018 Hsp70 is a molecular chaperone that binds to "client" proteins and protects them from protein degradation. Hsp70 is essential for the survival of many cancer cells, but it is not yet clear which of its clients are involved. Using structurally distinct chem ... Full text Link to item Cite

IAPs protect host target tissues from graft-versus-host disease in mice.

Journal Article Blood Adv · August 22, 2017 Inhibitors of apoptosis proteins (IAPs) regulate apoptosis, but little is known about the role of IAPs in the regulation of immunity. Development of IAP inhibition by second mitochondria-derived activator of caspase (SMAC) mimetics is emerging as a novel t ... Full text Link to item Cite

Targeting Inhibitor of Apoptosis Proteins Protects from Bleomycin-Induced Lung Fibrosis.

Journal Article Am J Respir Cell Mol Biol · April 2016 Accumulation of apoptosis-resistant fibroblasts is a hallmark of pulmonary fibrosis. We hypothesized that disruption of inhibitor of apoptosis protein (IAP) family proteins would limit lung fibrosis. We first show that transforming growth factor-β1 and ble ... Full text Link to item Cite

Inhibitor of apoptosis proteins as intracellular signaling intermediates.

Journal Article FEBS J · January 2016 Inhibitor of apoptosis (IAP) proteins have often been considered inhibitors of cell death due to early reports that described their ability to directly bind and inhibit caspases, the primary factors that implement apoptosis. However, a greater understandin ... Full text Link to item Cite

Effects of physiological and synthetic IAP antagonism on c-IAP-dependent signaling.

Journal Article Oncogene · October 2015 Cellular inhibitor of apoptosis proteins 1 and 2 (c-IAP1/2) have central roles in signal transduction mediated by numerous receptors that participate in inflammatory and immune responses. In certain pathways, such as activation of NF-κB, their degradation ... Full text Link to item Cite

Copper is a potent inhibitor of both the canonical and non-canonical NFκB pathways.

Journal Article Cell Cycle · 2014 Copper is an essential trace element that plays key roles in many metabolic processes. Homeostatic regulation of intracellular copper is normally tightly controlled, but deregulated copper levels are found in numerous metabolic and neurodegenerative diseas ... Full text Link to item Cite

Distinctive effects of the cellular inhibitor of apoptosis protein c-IAP2 through stabilization by XIAP in glioblastoma multiforme cells.

Journal Article Cell Cycle · 2014 Inhibitor of apoptosis proteins (IAPs) are extensively involved in NFκB signaling pathways. Regulation of c-IAP2 turnover by other proteins was investigated in glioblastoma multiforme (GBM) cells in the present study. When overexpressed, X-linked IAP (XIAP ... Full text Link to item Cite

IAP proteins: regulators of cell migration and development.

Journal Article Curr Opin Cell Biol · December 2012 The cytoprotective properties of vertebrate inhibitor of apoptosis (IAP) proteins have been the subject of much study. These proteins have, however, emerged as key signaling intermediates modulating a variety of cellular functions through their ability to ... Full text Link to item Cite

An inactivating caspase 11 passenger mutation originating from the 129 murine strain in mice targeted for c-IAP1.

Journal Article Biochem J · April 15, 2012 A recent study revealed that ES (embryonic stem) cell lines derived from the 129 murine strain carry an inactivating mutation within the caspase 11 gene (Casp4) locus [Kayagaki, Warming, Lamkanfi, Vande Walle, Louie, Dong, Newton, Qu, Liu, Heldens, Zhang, ... Full text Link to item Cite

Identifying the trigger of c-IAPs: structural and functional characterization of CARD-mediated modulation of ubiquitin ligase activity.

Journal Article Mol Cell · June 10, 2011 In this issue of Molecular Cell, Lopez et al. (2011) examine the caspase-recruitment domain (CARD) of c-IAP1 to reveal an intriguing mechanism in which conformational changes of the CARD determine c-IAP1's ubiquitin ligase activity, with implications for r ... Full text Link to item Cite

Regulation of the copper chaperone CCS by XIAP-mediated ubiquitination.

Journal Article Mol Cell Biol · April 2010 In order to balance the cellular requirements for copper with its toxic properties, an elegant set of mechanisms has evolved to regulate and buffer intracellular copper. The X-linked inhibitor of apoptosis (XIAP) protein was recently identified as a copper ... Full text Link to item Cite

XIAP as a ubiquitin ligase in cellular signaling.

Journal Article Cell Death Differ · January 2010 The ability of the vertebrate X-linked inhibitor of apoptosis (XIAP) protein to directly suppress apoptotic cell death pathways has been the subject of much research. Studies of this broadly expressed protein have largely focused on the unique interactions ... Full text Link to item Cite

Enhanced cytoprotective effects of the inhibitor of apoptosis protein cellular IAP1 through stabilization with TRAF2.

Journal Article J Biol Chem · July 31, 2009 Inhibitor of apoptosis (IAP) proteins are key regulators of intracellular signaling that interact with tumor necrosis factor (TNF) receptor superfamily members as well as proapoptotic molecules such as Smac/DIABLO and caspases. Whereas the X-linked IAP is ... Full text Link to item Cite

The E3 ubiquitin ligase cIAP1 binds and ubiquitinates caspase-3 and -7 via unique mechanisms at distinct steps in their processing.

Journal Article J Biol Chem · May 8, 2009 Inhibitor of apoptosis (IAP) proteins are widely expressed throughout nature and suppress cell death under a variety of circumstances. X-linked IAP, the prototypical IAP in mammals, inhibits apoptosis largely through direct inhibition of the initiator casp ... Full text Link to item Cite

Two distinct signalling cascades target the NF-kappaB regulatory factor c-IAP1 for degradation.

Journal Article Biochem J · April 28, 2009 c-IAP1 (cellular inhibitor of apoptosis 1) has recently emerged as a negative regulator of the non-canonical NF-kappaB (nuclear factor kappaB) signalling cascade. Whereas synthetic IAP inhibitors have been shown to trigger the autoubiquitination and degrad ... Full text Link to item Cite

A caspase homolog keeps CED-3 in check.

Journal Article Trends Biochem Sci · March 2009 Apoptosis is a highly conserved form of cell death that is essential for controlling cell numbers throughout the lifetime of an organism. In Caenorhabditis elegans, the final step in the apoptotic cascade is activation of the death-inducing protease CED-3. ... Full text Link to item Cite

Cytoprotective effects of IAPs revealed by a small molecule antagonist.

Journal Article Biochem J · February 1, 2009 Deregulated expression of members of the IAP (inhibitor of apoptosis) family has been identified in a wide variety of neoplastic cells, and synthetic IAP antagonists represent a promising novel class of chemotherapeutic agents. Early work focused on the ab ... Full text Link to item Cite

The aryl hydrocarbon nuclear translocator alters CD30-mediated NF-kappaB-dependent transcription.

Journal Article Science · January 9, 2009 Expression and signaling of CD30, a tumor necrosis factor receptor family member, is up-regulated in numerous lymphoid-derived neoplasias, most notably anaplastic large-cell lymphoma (ALCL) and Hodgkin's lymphoma. To gain insight into the mechanism of CD30 ... Full text Link to item Cite

Phenotypic differences between mice deficient in XIAP and SAP, two factors targeted in X-linked lymphoproliferative syndrome (XLP).

Journal Article Cell Immunol · 2009 Mutations in the X-linked inhibitor of apoptosis (XIAP) have recently been identified in patients with the rare genetic disease, X-linked lymphoproliferative syndrome (XLP), which was previously thought to be solely attributable to mutations in a distinct ... Full text Link to item Cite

Molecular mechanisms of cell death: recommendations of the Nomenclature Committee on Cell Death 2018.

Journal Article Cell Death Differ · March 2018 Over the past decade, the Nomenclature Committee on Cell Death (NCCD) has formulated guidelines for the definition and interpretation of cell death from morphological, biochemical, and functional perspectives. Since the field continues to expand and novel ... Full text Open Access Link to item Cite

Heat Shock Protein 70 (Hsp70) Suppresses RIP1-Dependent Apoptotic and Necroptotic Cascades.

Journal Article Mol Cancer Res · January 2018 Hsp70 is a molecular chaperone that binds to "client" proteins and protects them from protein degradation. Hsp70 is essential for the survival of many cancer cells, but it is not yet clear which of its clients are involved. Using structurally distinct chem ... Full text Link to item Cite

IAPs protect host target tissues from graft-versus-host disease in mice.

Journal Article Blood Adv · August 22, 2017 Inhibitors of apoptosis proteins (IAPs) regulate apoptosis, but little is known about the role of IAPs in the regulation of immunity. Development of IAP inhibition by second mitochondria-derived activator of caspase (SMAC) mimetics is emerging as a novel t ... Full text Link to item Cite

Targeting Inhibitor of Apoptosis Proteins Protects from Bleomycin-Induced Lung Fibrosis.

Journal Article Am J Respir Cell Mol Biol · April 2016 Accumulation of apoptosis-resistant fibroblasts is a hallmark of pulmonary fibrosis. We hypothesized that disruption of inhibitor of apoptosis protein (IAP) family proteins would limit lung fibrosis. We first show that transforming growth factor-β1 and ble ... Full text Link to item Cite

Inhibitor of apoptosis proteins as intracellular signaling intermediates.

Journal Article FEBS J · January 2016 Inhibitor of apoptosis (IAP) proteins have often been considered inhibitors of cell death due to early reports that described their ability to directly bind and inhibit caspases, the primary factors that implement apoptosis. However, a greater understandin ... Full text Link to item Cite

Effects of physiological and synthetic IAP antagonism on c-IAP-dependent signaling.

Journal Article Oncogene · October 2015 Cellular inhibitor of apoptosis proteins 1 and 2 (c-IAP1/2) have central roles in signal transduction mediated by numerous receptors that participate in inflammatory and immune responses. In certain pathways, such as activation of NF-κB, their degradation ... Full text Link to item Cite

Copper is a potent inhibitor of both the canonical and non-canonical NFκB pathways.

Journal Article Cell Cycle · 2014 Copper is an essential trace element that plays key roles in many metabolic processes. Homeostatic regulation of intracellular copper is normally tightly controlled, but deregulated copper levels are found in numerous metabolic and neurodegenerative diseas ... Full text Link to item Cite

Distinctive effects of the cellular inhibitor of apoptosis protein c-IAP2 through stabilization by XIAP in glioblastoma multiforme cells.

Journal Article Cell Cycle · 2014 Inhibitor of apoptosis proteins (IAPs) are extensively involved in NFκB signaling pathways. Regulation of c-IAP2 turnover by other proteins was investigated in glioblastoma multiforme (GBM) cells in the present study. When overexpressed, X-linked IAP (XIAP ... Full text Link to item Cite

IAP proteins: regulators of cell migration and development.

Journal Article Curr Opin Cell Biol · December 2012 The cytoprotective properties of vertebrate inhibitor of apoptosis (IAP) proteins have been the subject of much study. These proteins have, however, emerged as key signaling intermediates modulating a variety of cellular functions through their ability to ... Full text Link to item Cite

An inactivating caspase 11 passenger mutation originating from the 129 murine strain in mice targeted for c-IAP1.

Journal Article Biochem J · April 15, 2012 A recent study revealed that ES (embryonic stem) cell lines derived from the 129 murine strain carry an inactivating mutation within the caspase 11 gene (Casp4) locus [Kayagaki, Warming, Lamkanfi, Vande Walle, Louie, Dong, Newton, Qu, Liu, Heldens, Zhang, ... Full text Link to item Cite

Identifying the trigger of c-IAPs: structural and functional characterization of CARD-mediated modulation of ubiquitin ligase activity.

Journal Article Mol Cell · June 10, 2011 In this issue of Molecular Cell, Lopez et al. (2011) examine the caspase-recruitment domain (CARD) of c-IAP1 to reveal an intriguing mechanism in which conformational changes of the CARD determine c-IAP1's ubiquitin ligase activity, with implications for r ... Full text Link to item Cite

Regulation of the copper chaperone CCS by XIAP-mediated ubiquitination.

Journal Article Mol Cell Biol · April 2010 In order to balance the cellular requirements for copper with its toxic properties, an elegant set of mechanisms has evolved to regulate and buffer intracellular copper. The X-linked inhibitor of apoptosis (XIAP) protein was recently identified as a copper ... Full text Link to item Cite

XIAP as a ubiquitin ligase in cellular signaling.

Journal Article Cell Death Differ · January 2010 The ability of the vertebrate X-linked inhibitor of apoptosis (XIAP) protein to directly suppress apoptotic cell death pathways has been the subject of much research. Studies of this broadly expressed protein have largely focused on the unique interactions ... Full text Link to item Cite

Enhanced cytoprotective effects of the inhibitor of apoptosis protein cellular IAP1 through stabilization with TRAF2.

Journal Article J Biol Chem · July 31, 2009 Inhibitor of apoptosis (IAP) proteins are key regulators of intracellular signaling that interact with tumor necrosis factor (TNF) receptor superfamily members as well as proapoptotic molecules such as Smac/DIABLO and caspases. Whereas the X-linked IAP is ... Full text Link to item Cite

The E3 ubiquitin ligase cIAP1 binds and ubiquitinates caspase-3 and -7 via unique mechanisms at distinct steps in their processing.

Journal Article J Biol Chem · May 8, 2009 Inhibitor of apoptosis (IAP) proteins are widely expressed throughout nature and suppress cell death under a variety of circumstances. X-linked IAP, the prototypical IAP in mammals, inhibits apoptosis largely through direct inhibition of the initiator casp ... Full text Link to item Cite

Two distinct signalling cascades target the NF-kappaB regulatory factor c-IAP1 for degradation.

Journal Article Biochem J · April 28, 2009 c-IAP1 (cellular inhibitor of apoptosis 1) has recently emerged as a negative regulator of the non-canonical NF-kappaB (nuclear factor kappaB) signalling cascade. Whereas synthetic IAP inhibitors have been shown to trigger the autoubiquitination and degrad ... Full text Link to item Cite

A caspase homolog keeps CED-3 in check.

Journal Article Trends Biochem Sci · March 2009 Apoptosis is a highly conserved form of cell death that is essential for controlling cell numbers throughout the lifetime of an organism. In Caenorhabditis elegans, the final step in the apoptotic cascade is activation of the death-inducing protease CED-3. ... Full text Link to item Cite

Cytoprotective effects of IAPs revealed by a small molecule antagonist.

Journal Article Biochem J · February 1, 2009 Deregulated expression of members of the IAP (inhibitor of apoptosis) family has been identified in a wide variety of neoplastic cells, and synthetic IAP antagonists represent a promising novel class of chemotherapeutic agents. Early work focused on the ab ... Full text Link to item Cite

The aryl hydrocarbon nuclear translocator alters CD30-mediated NF-kappaB-dependent transcription.

Journal Article Science · January 9, 2009 Expression and signaling of CD30, a tumor necrosis factor receptor family member, is up-regulated in numerous lymphoid-derived neoplasias, most notably anaplastic large-cell lymphoma (ALCL) and Hodgkin's lymphoma. To gain insight into the mechanism of CD30 ... Full text Link to item Cite

Phenotypic differences between mice deficient in XIAP and SAP, two factors targeted in X-linked lymphoproliferative syndrome (XLP).

Journal Article Cell Immunol · 2009 Mutations in the X-linked inhibitor of apoptosis (XIAP) have recently been identified in patients with the rare genetic disease, X-linked lymphoproliferative syndrome (XLP), which was previously thought to be solely attributable to mutations in a distinct ... Full text Link to item Cite

Caspases and IAPs: a dance of death ensures cell survival.

Journal Article Mol Cell · November 21, 2008 In this issue of Molecular Cell, Ditzel et al. (2008) show that DIAP1 polyubiquitinates DRONC, DCP-1, and drICE, leading to their nondegradative inactivation. Surprisingly, activation of DIAP1 requires caspase-mediated cleavage, revealing an elegant feedba ... Full text Link to item Cite

Diverse functions within the IAP family.

Journal Article J Cell Sci · November 1, 2008 Full text Link to item Cite

Inhibitor of apoptosis proteins in eukaryotic evolution and development: a model of thematic conservation.

Journal Article Dev Cell · October 2008 The past decade and a half has witnessed the discovery of a large, evolutionarily conserved family of cellular genes bearing homology to the prototype baculovirus Inhibitor of Apoptosis (IAP). The logical decision in the field to also refer to these cellul ... Full text Link to item Cite

Apoptotic sensitivity of murine IAP-deficient cells.

Journal Article Biochem J · October 1, 2008 Although numerous studies have implicated the IAPs (inhibitor of apoptosis proteins) in the control of apoptotic cell death, analyses of murine Iap-targeted cells have not revealed significant differences in their susceptibility to apoptosis. In the presen ... Full text Link to item Cite

XIAP regulates cytosol-specific innate immunity to Listeria infection.

Journal Article PLoS Pathog · August 29, 2008 The inhibitor of apoptosis protein (IAP) family has been implicated in immune regulation, but the mechanisms by which IAP proteins contribute to immunity are incompletely understood. We show here that X-linked IAP (XIAP) is required for innate immune contr ... Full text Link to item Cite

X-linked inhibitor of apoptosis deficiency in the TRAMP mouse prostate cancer model.

Journal Article Cell Death Differ · May 2008 Deregulation of apoptotic pathways plays a central role in cancer pathogenesis. X-linked inhibitor of apoptosis protein (XIAP), is an antiapoptotic molecule, whose elevated expression has been observed in tumor specimens from patients with prostate carcino ... Full text Link to item Cite

EZH2 regulates the transcription of estrogen-responsive genes through association with REA, an estrogen receptor corepressor.

Journal Article Breast Cancer Res Treat · January 2008 Enhancer of zeste homolog 2 (EZH2) is a histone methyltransferase polycomb group (PcG) protein, which has been implicated in the process of cellular differentiation and cancer progression for both breast and prostate cancer. Although transcriptional repres ... Full text Link to item Cite

Apoptosis-inducing factor is a target for ubiquitination through interaction with XIAP.

Journal Article Mol Cell Biol · January 2008 X-linked inhibitor of apoptosis (XIAP) is an inhibitor of apoptotic cell death that protects cells by caspase-dependent and independent mechanisms. In a screen for molecules that participate with XIAP in regulating cellular activities, we identified apopto ... Full text Link to item Cite

New insights into the function of IAP proteins: modulation of the MYC/MAX/MAD network.

Journal Article Dev Cell · January 2008 A growing number of studies have revealed that the inhibitor of apoptosis (IAP) proteins play a variety of cellular roles in addition to suppression of apoptosis. A recent study in Molecular Cell demonstrates that one IAP member, c-IAP1, functions to poten ... Full text Link to item Cite

XIAP: cell death regulation meets copper homeostasis.

Journal Article Arch Biochem Biophys · July 15, 2007 X-linked inhibitor of apoptosis (XIAP), traditionally known as an anti-apoptotic protein, has recently been shown to be involved in copper homeostasis. XIAP promotes the ubiquitination and degradation of COMMD1, a protein that promotes the efflux of copper ... Full text Link to item Cite

CD30 activates both the canonical and alternative NF-kappaB pathways in anaplastic large cell lymphoma cells.

Journal Article J Biol Chem · April 6, 2007 CD30 is a member of the tumor necrosis factor receptor superfamily whose expression is up-regulated on anaplastic large cell lymphoma (ALCL) and Hodgkin lymphoma (HL) cells. Many different outcomes of CD30 stimulation have been reported, including cell cyc ... Full text Link to item Cite

Characterization of COMMD protein-protein interactions in NF-kappaB signalling.

Journal Article Biochem J · August 15, 2006 COMMD [copper metabolism gene MURR1 (mouse U2af1-rs1 region 1) domain] proteins constitute a recently identified family of NF-kappaB (nuclear factor kappaB)-inhibiting proteins, characterized by the presence of the COMM domain. In the present paper, we rep ... Full text Link to item Cite

Xaf1 can cooperate with TNFalpha in the induction of apoptosis, independently of interaction with XIAP.

Journal Article Mol Cell Biochem · June 2006 XIAP-associated factor 1 (Xaf1) binds XIAP and re-localizes it to the nucleus, thus inhibiting XIAP activity and enhancing apoptosis [1]. Xaf1 expression is reduced or absent in tumor samples and cell lines suggesting it may function as a tumor suppressor ... Full text Link to item Cite

XIAP Is a copper binding protein deregulated in Wilson's disease and other copper toxicosis disorders.

Journal Article Mol Cell · March 17, 2006 X-linked inhibitor of apoptosis (XIAP), known primarily for its caspase inhibitory properties, has recently been shown to interact with and regulate the levels of COMMD1, a protein associated with a form of canine copper toxicosis. Here, we describe a role ... Full text Link to item Cite

Reawakening the cellular death program in neoplasia through the therapeutic blockade of IAP function.

Journal Article J Clin Invest · October 2005 Recent studies have shown that members of the inhibitor of apoptosis (IAP) protein family are highly expressed in several classes of cancer. The primary implication of these findings is that the elevated expression of IAPs is not coincidental but actually ... Full text Link to item Cite

Constitutive proteasome-mediated turnover of Bfl-1/A1 and its processing in response to TNF receptor activation in FL5.12 pro-B cells convert it into a prodeath factor.

Journal Article Cell Death Differ · September 2005 Bfl-1/A1 is generally recognized as a Bcl-2-related inhibitor of apoptosis. We show that Bfl-1 undergoes constitutive ubiquitin/proteasome-mediated turnover. Moreover, while Bfl-1 suppresses apoptosis induced by staurosporine or cytokine withdrawal, it is ... Full text Link to item Cite

COMMD proteins, a novel family of structural and functional homologs of MURR1.

Journal Article J Biol Chem · June 10, 2005 MURR1 is a multifunctional protein that inhibits nuclear factor kappaB (NF-kappaB), a transcription factor with pleiotropic functions affecting innate and adaptive immunity, apoptosis, cell cycle regulation, and oncogenesis. Here we report the discovery of ... Full text Link to item Cite

The small heat shock protein alpha B-crystallin is a novel inhibitor of TRAIL-induced apoptosis that suppresses the activation of caspase-3.

Journal Article J Biol Chem · March 25, 2005 Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is a member of the tumor necrosis factor alpha family of cytokines that preferentially induces apoptosis in transformed cells, making it a promising cancer therapy. However, many neoplasms are ... Full text Link to item Cite

Differential role for TLR3 in respiratory syncytial virus-induced chemokine expression.

Journal Article J Virol · March 2005 Respiratory syncytial virus (RSV) is the leading cause of lower respiratory tract infection in young infants worldwide. Previous studies have reported that the induction of interleukin-8/CXCL8 and RANTES/CCL5 correlates with disease severity in humans. The ... Full text Link to item Cite

IAP proteins: sticking it to Smac.

Journal Article Biochem J · January 1, 2005 Dogma has it that suppression of the programmed cell death pathway by the IAP (inhibitor of apoptosis) proteins is achieved by their direct enzymic inhibition of the chief executioners of the apoptotic process, the caspases. In turn, the IAPs themselves ca ... Full text Link to item Cite

VIAF, a conserved inhibitor of apoptosis (IAP)-interacting factor that modulates caspase activation.

Journal Article J Biol Chem · December 3, 2004 Inhibitor of apoptosis (IAP) proteins are involved in the suppression of apoptosis, signal transduction, cell cycle control and gene regulation. Here we describe the cloning and characterization of viral IAP-associated factor (VIAF), a highly conserved, ub ... Full text Link to item Cite

Upstream regulatory role for XIAP in receptor-mediated apoptosis.

Journal Article Mol Cell Biol · August 2004 X-linked inhibitor of apoptosis (XIAP) is an endogenous inhibitor of cell death that functions by suppressing caspases 3, 7, and 9. Here we describe the establishment of Jurkat-derived cell lines stably overexpressing either full-length XIAP or a truncatio ... Full text Link to item Cite

Smac/Diablo antagonizes ubiquitin ligase activity of inhibitor of apoptosis proteins.

Journal Article J Biol Chem · June 25, 2004 Inhibitor of apoptosis proteins (IAPs) can block apoptosis through binding to active caspases and antagonizing their function. IAP function can be neutralized by Smac/Diablo, an IAP-binding protein that is released from mitochondria during apoptosis. In ad ... Full text Link to item Cite

Uncoupling of the signaling and caspase-inhibitory properties of X-linked inhibitor of apoptosis.

Journal Article J Biol Chem · March 5, 2004 In addition to its well described function as an enzymatic inhibitor of specific caspases, X-linked inhibitor of apoptosis (X-linked IAP or XIAP) can function as a cofactor in Smad, NF-kappaB, and JNK signaling pathways. However, caspases themselves have b ... Full text Link to item Cite

An alternative splice form of Mdm2 induces p53-independent cell growth and tumorigenesis.

Journal Article J Biol Chem · February 6, 2004 The Mdm2 gene is amplified in approximately one-third of human sarcomas and overexpressed in a variety of other human cancers. Mdm2 functions as an oncoprotein, in part, by acting as a negative regulator of the p53 tumor suppressor protein. Multiple splice ... Full text Link to item Cite

Acute ablation of survivin uncovers p53-dependent mitotic checkpoint functions and control of mitochondrial apoptosis.

Journal Article J Biol Chem · January 16, 2004 Survivin is a member of the Inhibitor of Apoptosis gene family that has been implicated in cell division and suppression of apoptosis. Here, we show that preferential ablation of the nuclear pool of survivin by RNA interference produces a mitotic arrest fo ... Full text Link to item Cite

A novel role for XIAP in copper homeostasis through regulation of MURR1.

Journal Article EMBO J · January 14, 2004 XIAP is a potent suppressor of apoptosis that directly inhibits specific members of the caspase family of cysteine proteases. Here we demonstrate a novel role for XIAP in the control of intracellular copper levels. XIAP was found to interact with MURR1, a ... Full text Link to item Cite

The gene product Murr1 restricts HIV-1 replication in resting CD4+ lymphocytes.

Journal Article Nature · December 18, 2003 Although human immunodeficiency virus-1 (HIV-1) infects quiescent and proliferating CD4+ lymphocytes, the virus replicates poorly in resting T cells. Factors that block viral replication in these cells might help to prolong the asymptomatic phase of HIV in ... Full text Link to item Cite

Dying for NF-kappaB? Control of cell death by transcriptional regulation of the apoptotic machinery.

Journal Article Curr Opin Cell Biol · December 2003 The transcription factor nuclear factor kappaB (NF-kappaB) is a pleiotropic protein complex that is activated from a sequestered, cytoplasmic form by pro-inflammatory extracellular signals and cellular stress. Several hundred cellular genes have been shown ... Full text Link to item Cite

Identification of ubiquitination sites on the X-linked inhibitor of apoptosis protein.

Journal Article Biochem J · August 1, 2003 The execution phase of apoptosis is under the control of members of the inhibitor of apoptosis (IAP) family of zinc finger proteins. Several of these proteins contain a C-terminal RING (really interesting new gene) domain that has been postulated to regula ... Full text Link to item Cite

A novel ubiquitin fusion system bypasses the mitochondria and generates biologically active Smac/DIABLO.

Journal Article J Biol Chem · February 28, 2003 Smac/DIABLO is a mitochondrial protein that is proteolytically processed and released during apoptosis along with cytochrome c and other proapoptotic factors. Once in the cytosol, Smac protein binds to inhibitors of apoptosis (IAP) proteins and disrupts th ... Full text Link to item Cite

XIAP inhibition of caspase-3 preserves its association with the Apaf-1 apoptosome and prevents CD95- and Bax-induced apoptosis.

Journal Article Cell Death Differ · September 2002 Ligation of death receptors or formation of the Apaf-1 apoptosome results in the activation of caspases and execution of apoptosis. We recently demonstrated that X-linked inhibitor-of-apoptosis protein (XIAP) associates with the apoptosome in vitro. By uti ... Full text Link to item Cite

IAP proteins: blocking the road to death's door.

Journal Article Nat Rev Mol Cell Biol · June 2002 The 'inhibitor of apoptosis' (IAP) gene family, which was discovered less than a decade ago, encodes a group of structurally related proteins that, in addition to their ability to suppress apoptotic cell death, are involved in an increasing number of seemi ... Full text Link to item Cite

Apoptosis and NF-kappa B: the FADD connection.

Journal Article J Clin Invest · March 2002 Full text Link to item Cite

Improvement of polynomial methods for reproducing functional dependences

Journal Article Measurement Techniques · January 1, 2002 A comparative analysis is made of polynomial methods of reproducing functions. Recommendations on reducing the errors and/or increasing the interpolation interval for Newton polynomials are proposed in a general form. The comparative analysis with the prac ... Full text Cite

SNIP1 inhibits NF-kappa B signaling by competing for its binding to the C/H1 domain of CBP/p300 transcriptional co-activators.

Journal Article J Biol Chem · December 7, 2001 SNIP1 is a 396-amino acid nuclear protein shown to be an inhibitor of the TGF-beta signal transduction pathway and to be important in suppressing transcriptional activation dependent on the co-activators CBP and p300. In this report we show that SNIP1 pote ... Full text Link to item Cite

X-linked inhibitor of apoptosis protein functions as a cofactor in transforming growth factor-beta signaling.

Journal Article J Biol Chem · July 13, 2001 X-linked inhibitor of apoptosis protein (XIAP) is a potent suppressor of apoptotic cell death, which functions by directly inhibiting caspases, the principal effectors of apoptosis. Here we report that XIAP can also function as a cofactor in the regulation ... Full text Link to item Cite

Distinct interactions of the X-linked lymphoproliferative syndrome gene product SAP with cytoplasmic domains of members of the CD2 receptor family.

Journal Article Clin Immunol · July 2001 X-linked lymphoproliferative syndrome (XLP; Duncan's disease) is a primary immunodeficiency disease that manifests as an inability to regulate the immune response to Epstein-Barr virus (EBV) infection. Here we examine the ability of the product of the gene ... Full text Link to item Cite

Molecular cloning of ILP-2, a novel member of the inhibitor of apoptosis protein family.

Journal Article Mol Cell Biol · July 2001 Inhibitor of apoptosis protein (IAP)-like protein-1 (ILP-1) (also known as X-linked IAP [XIAP] and mammalian IAP homolog A [MIHA]) is a potent inhibitor of apoptosis and exerts its effects, at least in part, by the direct association with and inhibition of ... Full text Link to item Cite

Altered lymphocyte responses and cytokine production in mice deficient in the X-linked lymphoproliferative disease gene SH2D1A/DSHP/SAP.

Journal Article Proc Natl Acad Sci U S A · June 19, 2001 We have introduced a targeted mutation in SH2D1A/DSHP/SAP, the gene responsible for the human genetic disorder X-linked lymphoproliferative disease (XLP). SLAM-associated protein (SAP)-deficient mice had normal lymphocyte development, but on challenge with ... Full text Link to item Cite

Characterization of XIAP-deficient mice.

Journal Article Mol Cell Biol · May 2001 The inhibitor of apoptosis protein (IAP) family consists of a number of evolutionarily conserved proteins that function to inhibit programmed cell death. X-linked IAP (XIAP) was cloned due to its sequence homology with other family members and has previous ... Full text Link to item Cite

c-IAP1 is cleaved by caspases to produce a proapoptotic C-terminal fragment.

Journal Article J Biol Chem · March 9, 2001 Although human c-IAP1 and c-IAP2 have been reported to possess antiapoptotic activity against a variety of stimuli in several mammalian cell types, we observed that full-length c-IAP1 and c-IAP2 failed to protect cells from apoptosis induced by Bax overexp ... Full text Link to item Cite

Differential effects of CD30 activation in anaplastic large cell lymphoma and Hodgkin disease cells.

Journal Article Blood · December 15, 2000 CD30 is a member of the tumor necrosis factor (TNF) receptor superfamily that is expressed on activated lymphocytes, as well as on neoplastic cells of Hodgkin disease (HD) and anaplastic large cell lymphoma (ALCL). A number of reports have shown that, depe ... Link to item Cite

A novel mitochondrial septin-like protein, ARTS, mediates apoptosis dependent on its P-loop motif.

Journal Article Nat Cell Biol · December 2000 Here we describe a protein product of the human septin H5/PNUTL2/CDCrel2b gene, which we call ARTS (for apoptosis-related protein in the TGF-beta signalling pathway). ARTS is expressed in many cells and acts to enhance cell death induced by TGF-beta or, to ... Full text Link to item Cite

Patients with X-linked lymphoproliferative disease have a defect in 2B4 receptor-mediated NK cell cytotoxicity.

Journal Article Eur J Immunol · November 2000 Patients with the X-linked lymphoproliferative disorder (XLPD) are unable to control Epstein-Barr virus (EBV)-induced infections and lymphoproliferation. This disease is caused by a deficit of SAP, an adapter protein involved in the signal transduction of ... Full text Link to item Cite

The IAP proteins: caspase inhibitors and beyond.

Journal Article Sci STKE · August 8, 2000 Apoptosis, or programmed cell death, occurs as an outcome of signals that direct cells to perish. Whether initiated by specifically activated receptors or induced through viral infection, apoptosis is an important means by which organisms maintain health a ... Full text Link to item Cite

Structural basis for SH2D1A mutations in X-linked lymphoproliferative disease.

Journal Article Biochem Biophys Res Commun · March 5, 2000 X-linked lymphoproliferative disease (XLP) is a rare and severe immune deficiency, characterized by abnormal immune responses to the Epstein-Barr virus. Recently, the gene responsible for XLP, SH2D1A, has been identified and shown to code for a small cytop ... Full text Link to item Cite

Selective activation of JNK1 is necessary for the anti-apoptotic activity of hILP.

Journal Article Proc Natl Acad Sci U S A · May 26, 1998 The balance between the inductive signals and endogenous anti-apoptotic mechanisms determines whether or not programmed cell death occurs. The widely expressed inhibitor of apoptosis gene family includes three closely related mammalian proteins: c-IAP1, c- ... Full text Link to item Cite

Human IAP-like protein regulates programmed cell death downstream of Bcl-xL and cytochrome c.

Journal Article Mol Cell Biol · January 1998 The gene encoding human IAP-like protein (hILP) is one of several mammalian genes with sequence homology to the baculovirus inhibitor-of-apoptosis protein (iap) genes. Here we show that hILP can block apoptosis induced by a variety of extracellular stimuli ... Full text Link to item Cite

The IAP family of apoptotic regulators.

Journal Article Results Probl Cell Differ · 1998 Full text Link to item Cite

CD30-dependent degradation of TRAF2: implications for negative regulation of TRAF signaling and the control of cell survival.

Journal Article Genes Dev · November 1, 1997 CD30 is a cell-surface receptor that can augment lymphocyte activation and survival through its ability to induce the transcription factor NF-kappaB. CD30, however, has also been implicated in the induction of apoptotic cell death of lymphocytes. Here we s ... Full text Link to item Cite

The iap genes: unique arbitrators of cell death.

Journal Article Trends Cell Biol · September 1997 The iap family of anti-apoptotic genes, originally discovered in viruses, has grown considerably in the past two years with the addition of a number of evolutionary conserved cellular homologues. Although the mechanism(s) by which these novel proteins bloc ... Full text Link to item Cite

Interaction of CTLA-4 with the clathrin-associated protein AP50 results in ligand-independent endocytosis that limits cell surface expression.

Journal Article J Immunol · July 1, 1997 CTLA-4 is a lymphocyte cell surface receptor expressed by activated T cells that functions to down-regulate T cell responses induced by TCR and CD28 stimulation. Since CTLA-4 competes with CD28 for binding to the common ligands B7-1 and B7-2, the level of ... Link to item Cite

Induction of nuclear factor kappaB by the CD30 receptor is mediated by TRAF1 and TRAF2.

Journal Article Mol Cell Biol · March 1997 CD30 is a lymphoid cell-specific surface receptor which was originally identified as an antigen expressed on Hodgkin's lymphoma cells. Activation of CD30 induces the nuclear factor kappaB (NF-kappaB) transcription factor. In this study, we define the domai ... Full text Link to item Cite

A new family of apoptotic cell death inhibitors

Journal Article FASEB Journal · December 1, 1996 Apoptosis, or programmed cell death, is a process by which cells can be eliminated without eliciting an inflammatory immune response. This is the mechanism used to delete immature T cells in the thymus and to eliminate activated immune cells once they are ... Cite

Identification of proteins which interact with the cytoplasmic domain of CTLA-4

Journal Article FASEB Journal · December 1, 1996 CTLA-4 is a lymphocyte cell surface receptor which has sequence homology to the T cell costimulatory receptor CD28. Unlike CD28, CTLA-4 is expressed only upon T cell activation and appears to function as a negative regulator of T cell activation. How CTLA- ... Cite

A conserved family of cellular genes related to the baculovirus iap gene and encoding apoptosis inhibitors.

Journal Article EMBO J · June 3, 1996 The baculovirus inhibitor of apoptosis gene, iap, can impede cell death in insect cells. Here we show that iap can also prevent cell death in mammalian cells. The ability of iap to regulate programmed cell death in widely divergent species raised the possi ... Link to item Cite

CD30 contains two binding sites with different specificities for members of the tumor necrosis factor receptor-associated factor family of signal transducing proteins.

Journal Article J Biol Chem · May 31, 1996 CD30 is a member of the tumor necrosis factor (TNF) receptor family of proteins. CD30 can regulate proliferation of lymphocytes and may also play an important role in human immunodeficiency virus replication. However, little is known about CD30 signal tran ... Full text Link to item Cite

iPABP, an inducible poly(A)-binding protein detected in activated human T cells.

Journal Article Mol Cell Biol · December 1995 The poly(A)-binding protein (PABP) binds to the poly(A) tail present at the 3' ends of most eukaryotic mRNAs. PABP is thought to play a role in both translation and mRNA stability. Here we describe the molecular cloning and characterization of an inducible ... Full text Link to item Cite

Cytokine induction of nuclear factor kappa B in cycling and growth-arrested cells. Evidence for cell cycle-independent activation.

Journal Article J Biol Chem · August 11, 1995 Nuclear factor kappa B (NF-kappa B) is a pleiotropic transcription factor which regulates the expression of a large number of cellular and viral genes. Induction of NF-kappa B has been shown previously to occur during cell cycle transition from G0 to G1, b ... Full text Link to item Cite

Regulation of human retroviral latency by the NF-kappa B/I kappa B family: inhibition of human immunodeficiency virus replication by I kappa B through a Rev-dependent mechanism.

Journal Article Proc Natl Acad Sci U S A · February 28, 1995 The cellular transcription factor NF-kappa B stimulates human immunodeficiency virus type 1 (HIV-1) transcriptional initiation, but its role in the retroviral life cycle has not been fully defined. In this report, we show that I kappa B alpha acts as a cel ... Full text Link to item Cite

Transcription factor AP-2 regulates human immunodeficiency virus type 1 gene expression.

Journal Article J Virol · October 1994 Human immunodeficiency virus type 1 (HIV-1) gene expression is regulated by an enhancer region composed of multiple potential cis-acting regulatory sites. Here, we describe binding sites for the transcription factor AP-2 in the HIV-1 long terminal repeat w ... Full text Link to item Cite

Differential regulation of vascular cell adhesion molecule 1 gene expression by specific NF-kappa B subunits in endothelial and epithelial cells.

Journal Article Mol Cell Biol · October 1993 Vascular cell adhesion molecule 1 (VCAM-1) is expressed in both endothelial and epithelial cell types, where it contributes to lymphocyte migration to sites of inflammation. Its expression is regulated by cytokines, in part through two kappa B-like regulat ... Full text Link to item Cite

A cooperative interaction between NF-kappa B and Sp1 is required for HIV-1 enhancer activation.

Journal Article EMBO J · September 1993 The human immunodeficiency virus (HIV-1) long terminal repeat (LTR) contains two binding sites for NF-kappa B in close proximity to three binding sites for the constitutive transcription factor, Sp1. Previously, stimulation of the HIV enhancer in response ... Full text Link to item Cite

Dimerization of NF-KB2 with RelA(p65) regulates DNA binding, transcriptional activation, and inhibition by an I kappa B-alpha (MAD-3).

Journal Article Mol Cell Biol · March 1993 Inducible expression of human immunodeficiency virus (HIV) is regulated by a cellular transcription factor, nuclear factor kappa B (NF-kappa B). NF-kappa B is composed of distinct subunits; five independent genes, NFKB1(p105), NFKB2(p100), RelA(p65), c-rel ... Full text Link to item Cite

The proto-oncogene bcl-3 encodes an I kappa B protein.

Journal Article Genes Dev · December 1992 The bcl-3 gene product, overexpressed in chronic lymphocytic leukemia (CLL) patients with the translocation t(14;19), is a member of the I kappa B family. The bcl-3 protein is able to inhibit the DNA binding and trans-activation of authentic NF-kappa B het ... Full text Link to item Cite

Distinct combinations of NF-kappa B subunits determine the specificity of transcriptional activation.

Journal Article Proc Natl Acad Sci U S A · March 1, 1992 The nuclear factor that binds to the kappa light-chain enhancer of B cells (NF-kappa B) is a transcription factor that regulates the expression of a variety of cellular and viral genes. NF-kappa B is composed of distinct subunits, and at least four indepen ... Full text Link to item Cite

DNA CpG methylation inhibits binding of NF-kappa B proteins to the HIV-1 long terminal repeat cognate DNA motifs.

Journal Article New Biol · October 1991 The regulation of cellular or viral gene expression is directly influenced by the pattern of methylated cytosine residues localized in the DNA of enhancer/promoter sequences. The mechanism of transcriptional silencing has been explained on the basis of eit ... Link to item Cite

Cloning of an NF-kappa B subunit which stimulates HIV transcription in synergy with p65.

Journal Article Nature · August 22, 1991 The transcription factor NF-kappa B is a protein complex which comprises a DNA-binding subunit and an associated transactivation protein (of relative molecular masses 50,000 (50K) and 65K, respectively). Both the 50K and 65K subunits have similarity with t ... Full text Link to item Cite