Scholars@Duke
Francis Ka-Ming Chan

Francis Ka-Ming Chan

Adjunct Professor in the Department of Immunology
Integrative Immunobiology
franciskaming.chan@duke.edu
312 Jones Building, DUMC 3010, Durham, NC 27710
Jones 312, DUMC 3010, Durham, NC 27710

Selected Publications

Association of breast milk-derived arachidonic acid-induced infant gut dysbiosis with the onset of atopic dermatitis

Journal Article Gut · July 30, 2024 ObjectiveThe specific breast milk-derived metabolites that mediate host–microbiota interactions and contribute to the onset of atopic dermatitis (AD) remain unknown and require further investigation. Full text Cite

Necroptosis stimulates interferon-mediated protective anti-tumor immunity.

Journal Article Cell death & disease · June 2024 Necroptosis is an inflammatory form of cell suicide that critically depends on the kinase activity of Receptor Interacting Protein Kinase 3 (RIPK3). Previous studies showed that immunization with necroptotic cells conferred protection against subsequent tu ... Full text Cite

A second-generation M1-polarized CAR macrophage with antitumor efficacy.

Journal Article Nat Immunol · January 2024 Chimeric antigen receptor (CAR) T cell therapies have successfully treated hematological malignancies. Macrophages have also gained attention as an immunotherapy owing to their immunomodulatory capacity and ability to infiltrate solid tumors and phagocytiz ... Full text Link to item Cite

Necroptosis Stimulates Interferon-Mediated Protective Anti-Tumor Immunity.

Journal Article Res Sq · December 19, 2023 Necroptosis is an inflammatory form of cell suicide that critically depends on the kinase activity of Receptor Interacting Protein Kinase 3 (RIPK3). Previous studies showed that immunization with necroptotic cells conferred protection against subsequent tu ... Full text Link to item Cite

The Use of a Non-Invasive Biomarker for Colorectal Cancer Screening: A Comparative Cost-Effectiveness Modeling Study.

Journal Article Cancers (Basel) · January 19, 2023 This study aimed to examine the cost-effectiveness of fecal biomarker M3 panel compared to fecal immunochemical test (FIT) and colonoscopy in an Asian population. In a hypothetical population of 100,000 persons aged 50 years who received FIT yearly, M3 bio ... Full text Link to item Cite

Necroptosis at a glance.

Journal Article J Cell Sci · September 1, 2022 Necroptosis, or programmed necrosis, is an inflammatory form of cell death with important functions in host defense against pathogens and tissue homeostasis. The four cytosolic receptor-interacting protein kinase homotypic interaction motif (RHIM)-containi ... Full text Link to item Cite

Tumor-intrinsic and immune modulatory roles of receptor-interacting protein kinases.

Journal Article Trends Biochem Sci · April 2022 Receptor-interacting protein kinase 1 (RIPK1) and RIPK3 are signaling adaptors that critically regulate cell death and inflammation. Tumors have adapted to subvert RIPK-dependent cell death, suggesting that these processes have key roles in tumor regulatio ... Full text Link to item Cite

The scaffold-dependent function of RIPK1 in dendritic cells promotes injury-induced colitis.

Journal Article Mucosal Immunol · January 2022 Receptor interacting protein kinase 1 (RIPK1) is a cytosolic multidomain protein that controls cell life and death. While RIPK1 promotes cell death through its kinase activity, it also functions as a scaffold protein to promote cell survival by inhibiting ... Full text Link to item Cite

Generation of recombinant vaccinia virus and analysis of virus-induced cell death.

Journal Article STAR Protoc · December 17, 2021 Vaccinia virus is a large double-stranded DNA virus that is widely used to express foreign genes from different origins. We generated recombinant vaccinia virus that expresses a viral inhibitor to examine its effect on virus-induced necroptosis. We provide ... Full text Link to item Cite

Sweet modification and regulation of death receptor signalling pathway.

Journal Article J Biochem · September 7, 2021 Death receptors, members of the tumour necrosis factor receptor (TNFR) superfamily, are characterized by the presence of a death domain in the cytosolic region. TNFR1, Fas and TNF-related apoptosis-inducing ligand receptors, which are prototypical death re ... Full text Link to item Cite

A class of viral inducer of degradation of the necroptosis adaptor RIPK3 regulates virus-induced inflammation.

Journal Article Immunity · February 9, 2021 Featured Publication The vaccine strain against smallpox, vaccinia virus (VACV), is highly immunogenic yet causes relatively benign disease. These attributes are believed to be caused by gene loss in VACV. Using a targeted small interfering RNA (siRNA) screen, we identified a ... Full text Link to item Cite

Regulatory mechanisms of RIPK1 in cell death and inflammation.

Journal Article Semin Cell Dev Biol · January 2021 Featured Publication Receptor Interacting Protein Kinase 1 (RIPK1) and RIPK3 are key adaptors that play critical roles in inflammatory and cell death signaling. Work in recent years have shown that their activities are tightly regulated by ubiquitination, phosphorylation and p ... Full text Link to item Cite

The death-inducing activity of RIPK1 is regulated by the pH environment.

Journal Article Sci Signal · May 12, 2020 Featured Publication Receptor-interacting protein kinase 1 (RIPK1) is a serine/threonine kinase that dictates whether cells survive or die in response to the cytokine tumor necrosis factor (TNF) and other inflammatory stimuli. The activity of RIPK1 is tightly controlled by mul ... Full text Link to item Cite

Necroptosis in anti-viral inflammation.

Journal Article Cell Death Differ · January 2019 The primary function of the immune system is to protect the host from invading pathogens. In response, microbial pathogens have developed various strategies to evade detection and destruction by the immune system. This tug-of-war between the host and the p ... Full text Link to item Cite

Inflammasome, Inflammation, and Tissue Homeostasis.

Journal Article Trends Mol Med · March 2018 Organismal fitness demands proper response to neutralize the threat from infection or injury. At the mammalian intestinal epithelium barrier, the inflammasome coordinates an elaborate tissue repair response marked by the induction of antimicrobial peptides ... 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

Loss-of-Function RNAi Screen to Identify Necrosis-Signaling Molecules.

Journal Article Methods Mol Biol · 2018 Over the recent years, genome-wide RNA interference (RNAi) library screens have been instrumental in the identification of key regulators of various biological pathways. The prolific use of this technique is attributed to its amenability to a high-throughp ... Full text Link to item Cite

Leishmania braziliensis Subverts Necroptosis by Modulating RIPK3 Expression.

Journal Article Front Microbiol · 2018 Featured Publication Leishmania braziliensis infection causes skin ulcers, typically found in localized cutaneous leishmaniasis (LCL). This tissue pathology associates with different modalities of cell necrosis, which are subverted by the parasite as a survival strategy. Herei ... Full text Open Access Link to item Cite

RIPK1-RIPK3-MLKL-Associated Necroptosis Drives Leishmania infantum Killing in Neutrophils.

Journal Article Front Immunol · 2018 Necroptosis is a pro-inflammatory cell death, which happens in the context of caspase-8 inhibition, allowing activation of the receptor interacting protein kinase 1-receptor interacting protein kinase 3-mixed lineage kinase domain-like (RIPK1-RIPK3-MLKL) a ... Full text Link to item Cite

Peptidoglycan-Sensing Receptors Trigger the Formation of Functional Amyloids of the Adaptor Protein Imd to Initiate Drosophila NF-κB Signaling.

Journal Article Immunity · October 17, 2017 In the Drosophila immune response, bacterial derived diaminopimelic acid-type peptidoglycan binds the receptors PGRP-LC and PGRP-LE, which through interaction with the adaptor protein Imd leads to activation of the NF-κB homolog Relish and robust antimicro ... Full text Link to item Cite

Frontline Science: Multiple cathepsins promote inflammasome-independent, particle-induced cell death during NLRP3-dependent IL-1β activation.

Journal Article J Leukoc Biol · July 2017 Sterile particles cause several chronic, inflammatory diseases, characterized by repeating cycles of particle phagocytosis and inflammatory cell death. Recent studies have proposed that these processes are driven by the NLRP3 inflammasome, a platform activ ... Full text Link to item Cite

Bacterial pathogenesis: Pathogenic bacteria attack RHIM.

Journal Article Nat Microbiol · March 28, 2017 Attaching and effacing enteropathogenic Escherichia coli causes gastrointestinal inflammation and diarrhoea. In this issue of Nature Microbiology, Pearson and colleagues find that this pathology involves bacterial cleavage of a class of host cell death sig ... Full text Link to item Cite

Distinct Kinase-Independent Role of RIPK3 in CD11c+ Mononuclear Phagocytes in Cytokine-Induced Tissue Repair.

Journal Article Cell Rep · March 7, 2017 Featured Publication Receptor interacting protein kinase 3 (RIPK3) induces necroptosis, a type of regulated necrosis, through its kinase domain and receptor interacting protein (RIP) homotypic interaction motif (RHIM). In addition, RIPK3 has been shown to regulate NLRP3 inflam ... Full text Link to item Cite

Necroptosis: Mechanisms and Relevance to Disease.

Book · January 24, 2017 Necroptosis is a form of regulated cell death that critically depends on receptor-interacting serine-threonine kinase 3 (RIPK3) and mixed lineage kinase domain-like (MLKL) and generally manifests with morphological features of necrosis. The molecular mecha ... Full text Link to item Cite

The Inflammatory Signal Adaptor RIPK3: Functions Beyond Necroptosis.

Chapter · 2017 Receptor interacting protein kinase 3 (RIPK3) is an essential serine/threonine kinase for necroptosis, a type of regulated necrosis. A variety of stimuli can cause RIPK3 activation through phosphorylation. Activated RIPK3 in turn phosphorylates and activat ... Full text Link to item Cite

RIPK3 Slams the Brake on Leukemogenesis.

Journal Article Cancer Cell · July 11, 2016 Evasion of cell death is a key hallmark of cancers. In this issue of Cancer Cell, Höckendorf and colleagues identified RIPK3, an essential kinase for necroptosis, as having a key role in inhibiting acute myeloid leukemia development. ... Full text Link to item Cite

RIPK1 and PGAM5 Control Leishmania Replication through Distinct Mechanisms.

Journal Article J Immunol · June 15, 2016 Leishmaniasis is an important parasitic disease found in the tropics and subtropics. Cutaneous and visceral leishmaniasis affect an estimated 1.5 million people worldwide. Despite its human health relevance, relatively little is known about the cell death ... Full text Link to item Cite

Necroptosis-independent signaling by the RIP kinases in inflammation.

Journal Article Cell Mol Life Sci · June 2016 Recent advances have identified a signaling cascade involving receptor interacting protein kinase 1 (RIPK1), RIPK3 and the pseudokinase mixed lineage kinase domain-like (MLKL) that is crucial for induction of necroptosis, a non-apoptotic form of cell death ... Full text Link to item Cite

Regulation of RIPK3- and RHIM-dependent Necroptosis by the Proteasome.

Journal Article J Biol Chem · March 11, 2016 Featured Publication Receptor-interacting protein kinase 3 (RIPK3) is a serine/threonine kinase with essential function in necroptosis. The activity of RIPK3 is controlled by phosphorylation. Once activated, RIPK3 phosphorylates and activates the downstream effector mixed line ... Full text Link to item Cite

The Mitochondrial Phosphatase PGAM5 Is Dispensable for Necroptosis but Promotes Inflammasome Activation in Macrophages.

Journal Article J Immunol · January 1, 2016 Featured Publication The cytokine IL-1β is intimately linked to many pathological inflammatory conditions. Mature IL-1β secretion requires cleavage by the inflammasome. Recent evidence indicates that many cell death signal adaptors have regulatory roles in inflammasome activit ... Full text Link to item Cite

Border Security: The Role of RIPK3 in Epithelium Homeostasis.

Journal Article Front Cell Dev Biol · 2016 Receptor interacting protein kinase 3 (RIPK3) is a crucial inducer of necroptosis. Its activity is controlled by interaction with other signal adaptors through the "RIP homotypic interaction motif" (RHIM). Recent studies revealed a critical function for RI ... Full text Link to item Cite

A RIPK3-caspase 8 complex mediates atypical pro-IL-1β processing.

Journal Article J Immunol · February 15, 2015 Featured Publication Caspase 8, the initiator caspase for death receptor-induced apoptosis, functions as a negative regulator of receptor interacting protein kinase 3 (RIPK3), an essential factor for TNF-, TLR3-, and TLR4-induced necroptosis. In certain situations, caspase 8 c ... Full text Link to item Cite

Differential roles of RIPK1 and RIPK3 in TNF-induced necroptosis and chemotherapeutic agent-induced cell death.

Journal Article Cell Death Dis · February 12, 2015 Featured Publication Apoptosis is a key mechanism for metazoans to eliminate unwanted cells. Resistance to apoptosis is a hallmark of many cancer cells and a major roadblock to traditional chemotherapy. Recent evidence indicates that inhibition of caspase-dependent apoptosis s ... Full text Link to item Cite

Essential versus accessory aspects of cell death: recommendations of the NCCD 2015.

Journal Article Cell Death Differ · January 2015 Cells exposed to extreme physicochemical or mechanical stimuli die in an uncontrollable manner, as a result of their immediate structural breakdown. Such an unavoidable variant of cellular demise is generally referred to as 'accidental cell death' (ACD). I ... Full text Link to item Cite

Programmed necrosis in the cross talk of cell death and inflammation.

Chapter · 2015 Cell proliferation and cell death are integral elements in maintaining homeostatic balance in metazoans. Disease pathologies ensue when these processes are disturbed. A plethora of evidence indicates that malfunction of cell death can lead to inflammation, ... Full text Link to item Cite

RIP3 induces apoptosis independent of pronecrotic kinase activity.

Journal Article Mol Cell · November 20, 2014 Receptor-interacting protein kinase 3 (RIP3 or RIPK3) has emerged as a central player in necroptosis and a potential target to control inflammatory disease. Here, three selective small-molecule compounds are shown to inhibit RIP3 kinase-dependent necroptos ... Full text Link to item Cite

Programmed necrosis/necroptosis: An inflammatory form of cell death

Chapter · November 1, 2014 It was not long ago when necrosis was thought to be cell injury caused by nonspecific physical trauma. In recent years, a dedicated pathway that triggers necrosis in response to TNF-like death cytokines, certain toll-like receptors, and in response to vira ... Full text Cite

The necroptosis adaptor RIPK3 promotes injury-induced cytokine expression and tissue repair.

Journal Article Immunity · October 16, 2014 Featured Publication Programmed necrosis or necroptosis is an inflammatory form of cell death that critically requires the receptor-interacting protein kinase 3 (RIPK3). Here we showed that RIPK3 controls a separate, necrosis-independent pathway of inflammation by regulating c ... Full text Link to item Cite

Cutting edge: RIPK1 Kinase inactive mice are viable and protected from TNF-induced necroptosis in vivo.

Journal Article J Immunol · August 15, 2014 The serine/threonine kinase RIPK1 is recruited to TNFR1 to mediate proinflammatory signaling and to regulate TNF-induced cell death. A RIPK1 deficiency results in perinatal lethality, impaired NFκB and MAPK signaling, and sensitivity to TNF-induced apoptos ... Full text Link to item Cite

Caspase-8 and RIP kinases regulate bacteria-induced innate immune responses and cell death.

Journal Article Proc Natl Acad Sci U S A · May 20, 2014 A number of pathogens cause host cell death upon infection, and Yersinia pestis, infamous for its role in large pandemics such as the "Black Death" in medieval Europe, induces considerable cytotoxicity. The rapid killing of macrophages induced by Y. pestis ... Full text Link to item Cite

Staying alive: cell death in antiviral immunity.

Journal Article Mol Cell · April 24, 2014 Programmed cell death is an integral part of host defense against invading intracellular pathogens. Apoptosis, programmed necrosis, and pyroptosis each serve to limit pathogen replication in infected cells, while simultaneously promoting the inflammatory a ... Full text Link to item Cite

Necrosis-dependent and independent signaling of the RIP kinases in inflammation.

Conference Cytokine Growth Factor Rev · April 2014 It is now widely accepted that some forms of necrosis are controlled by a dedicated signaling pathway triggered by various cell surface and intracellular receptors. This regulated form of necrosis is mediated by the kinase activity of receptor-interacting ... Full text Link to item Cite

TNF-induced necroptosis and PARP-1-mediated necrosis represent distinct routes to programmed necrotic cell death.

Journal Article Cell Mol Life Sci · January 2014 Programmed necrosis is important in many (patho)physiological settings. For specific therapeutic intervention, however, a better knowledge is required whether necrosis occurs through one single "core program" or through several independent pathways. Previo ... Full text Link to item Cite

Positive and negative phosphorylation regulates RIP1- and RIP3-induced programmed necrosis.

Journal Article Biochem J · December 15, 2013 Programmed necrosis or necroptosis is controlled by the action of two serine/threonine kinases, RIP1 (receptor-interacting serine/threonine protein kinase 1; also known as RIPK1) and RIP3. The phosphorylation of RIP1 and RIP3 is critical for assembly of th ... Full text Link to item Cite

RIP3: a molecular switch for necrosis and inflammation.

Journal Article Genes Dev · August 1, 2013 The receptor-interacting protein kinase 3 (RIP3/RIPK3) has emerged as a critical regulator of programmed necrosis/necroptosis, an inflammatory form of cell death with important functions in pathogen-induced and sterile inflammation. RIP3 activation is tigh ... Full text Link to item Cite

CYLD deubiquitinates RIP1 in the TNFα-induced necrosome to facilitate kinase activation and programmed necrosis.

Journal Article PLoS One · 2013 Featured Publication BACKGROUND: Necroptosis/programmed necrosis is initiated by a macro-molecular protein complex termed the necrosome. Receptor interacting protein kinase 1 (RIPK1/RIP1) and RIP3 are key components of the necrosome. TNFα is a prototypic inducer of necrosome a ... Full text Link to item Cite

Detection of necrosis by release of lactate dehydrogenase activity.

Journal Article Methods Mol Biol · 2013 Apoptosis and necrosis are two major forms of cell death observed in normal and disease pathologies. Although there are many assays for detection of apoptosis, relatively few assays are available for measuring necrosis. A key signature for necrotic cells i ... Full text Link to item Cite

Fueling the flames: Mammalian programmed necrosis in inflammatory diseases.

Journal Article Cold Spring Harb Perspect Biol · November 1, 2012 Programmed necrosis or necroptosis is an inflammatory form of cell death driven by TNF-like death cytokines, toll-like receptors, and antigen receptors. Unlike necrosis induced by physical trauma, a dedicated pathway is involved in programmed necrosis. In ... Full text Link to item Cite

The RIP1/RIP3 necrosome forms a functional amyloid signaling complex required for programmed necrosis.

Journal Article Cell · July 20, 2012 Featured Publication RIP1 and RIP3 kinases are central players in TNF-induced programmed necrosis. Here, we report that the RIP homotypic interaction motifs (RHIMs) of RIP1 and RIP3 mediate the assembly of heterodimeric filamentous structures. The fibrils exhibit classical cha ... Full text Link to item Cite

Heme induces programmed necrosis on macrophages through autocrine TNF and ROS production.

Journal Article Blood · March 8, 2012 Diseases that cause hemolysis or myonecrosis lead to the leakage of large amounts of heme proteins. Free heme has proinflammatory and cytotoxic effects. Heme induces TLR4-dependent production of tumor necrosis factor (TNF), whereas heme cytotoxicity has be ... Full text Link to item Cite

RIP3 finds partners in crime.

Journal Article Cell · January 20, 2012 Programmed necrosis has long been recognized as a crucial component of animal development; however, the signaling pathway beyond the protein kinases RIP1 and RIP3 remains largely unknown. Sun et al. and Wang et al. now identify critical factors downstream ... Full text Link to item Cite

Functional complementation between FADD and RIP1 in embryos and lymphocytes.

Journal Article Nature · March 17, 2011 Featured Publication FADD is a common adaptor shared by several death receptors for signalling apoptosis through recruitment and activation of caspase 8 (refs 1-3). Death receptors are essential for immune homeostasis, but dispensable during embryogenesis. Surprisingly, Fadd(- ... Full text Link to item Cite

RIP1-dependent and independent effects of necrostatin-1 in necrosis and T cell activation.

Journal Article PLoS One · 2011 BACKGROUND: Programmed necrosis/necroptosis is an emerging form of cell death that plays important roles in mammalian development and the immune system. The pro-necrotic kinases in the receptor interacting protein (RIP) family are crucial mediators of prog ... Full text Link to item Cite

A RNA interference screen identifies RIP3 as an essential inducer of TNF-induced programmed necrosis.

Conference Adv Exp Med Biol · 2011 Recent evidence indicates that TNF-like death cytokines can induce apoptotic and non-apoptotic forms of cell death. We have coined the term “programmed necrosis” to describe caspase-independent cell death induced by TNF-like cytokines. Besides an obligate ... Full text Link to item Cite

Viral cell death inhibitor MC159 enhances innate immunity against vaccinia virus infection.

Journal Article J Virol · October 2010 Featured Publication Viral inhibitors of host programmed cell death (PCD) are widely believed to promote viral replication by preventing or delaying host cell death. Viral FLIPs (Fas-linked ICE-like protease [FLICE; caspase-8]-like inhibitor proteins) are potent inhibitors of ... Full text Link to item Cite

Going up in flames: necrotic cell injury and inflammatory diseases.

Journal Article Cell Mol Life Sci · October 2010 Recent evidence indicates that cell death can be induced through multiple mechanisms. Strikingly, the same death signal can often induce apoptotic as well as non-apoptotic cell death. For instance, inhibition of caspases often converts an apoptotic stimulu ... Full text Link to item Cite

The molecular regulation of programmed necrotic cell injury.

Journal Article Trends Biochem Sci · August 2010 Proper regulation of cell death is essential for metazoan development and functions. Unlike apoptosis, necrosis is a more inflammatory form of cell death that might contribute to antiviral immunity. Indeed, necrotic cell injury is distinguished from apopto ... Full text Link to item Cite

Lipopolysaccharide-induced expression of TRAIL promotes dendritic cell differentiation.

Journal Article Immunology · August 2010 Tumour necrosis factor-related apoptosis inducing ligand (TRAIL) is a death-inducing cytokine whose physiological function is not well understood. Here, we show that TRAIL has a role in programming human dendritic cell (DC) differentiation. TRAIL expressio ... Full text Link to item Cite

Physiological consequences of programmed necrosis, an alternative form of cell demise.

Journal Article Mol Cells · April 2010 Cell death occurs spontaneously or in response to external stimuli, and can be largely subdivided into apoptosis and necrosis by the distinct morphological and biochemical features. Unlike apoptosis, necrosis was recognized as the passive and unwanted cell ... Full text Link to item Cite

Phosphorylation-driven assembly of the RIP1-RIP3 complex regulates programmed necrosis and virus-induced inflammation.

Journal Article Cell · June 12, 2009 Featured Publication Programmed necrosis is a form of caspase-independent cell death whose molecular regulation is poorly understood. The kinase RIP1 is crucial for programmed necrosis, but also mediates activation of the prosurvival transcription factor NF-kappaB. We postulat ... Full text Link to item Cite

Three is better than one: pre-ligand receptor assembly in the regulation of TNF receptor signaling.

Journal Article Cytokine · February 2007 The tumor necrosis factor (TNF) family of cytokines and their receptors regulates many areas of metazoan biology. Specifically, this cytokine-receptor family plays crucial roles in regulating myriad aspects of immune development and functions. Disruption o ... Full text Link to item Cite

Detection of Protein-Protein Interactions in vivo Using Cyan and Yellow Fluorescent Proteins

Chapter · December 1, 2006 This article describes a technique for detecting protein?protein interactions in vivo using cyan and yellow fluorescent proteins. The phenomenon of fluorescence resonance energy transfer (FRET) describes the transfer of energy from one fluorophore to anoth ... Full text Cite

Transgenic expression of the viral FLIP MC159 causes lpr/gld-like lymphoproliferation and autoimmunity.

Journal Article J Immunol · September 15, 2006 Death receptor-induced programmed cell death (PCD) is crucial for the maintenance of immune homeostasis. However, interference of downstream death receptor signaling by genetic ablation or transgenic (Tg) expression of different apoptosis inhibitors often ... Full text Link to item Cite

Poxvirus tumor necrosis factor receptor (TNFR)-like T2 proteins contain a conserved preligand assembly domain that inhibits cellular TNFR1-induced cell death.

Journal Article J Virol · September 2006 The poxvirus tumor necrosis factor receptor (TNFR) homologue T2 has immunomodulatory properties; secreted myxoma virus T2 (M-T2) protein binds and inhibits rabbit TNF-alpha, while intracellular M-T2 blocks virus-induced lymphocyte apoptosis. Here, we defin ... Full text Link to item Cite

Competitive control of independent programs of tumor necrosis factor receptor-induced cell death by TRADD and RIP1.

Journal Article Mol Cell Biol · May 2006 Stimulation of tumor necrosis factor receptor 1 (TNFR1) can initiate several cellular responses, including apoptosis, which relies on caspases, necrotic cell death, which depends on receptor-interacting protein kinase 1 (RIP1), and NF-kappaB activation, wh ... Full text Link to item Cite

Preligand assembly domain-mediated ligand-independent association between TRAIL receptor 4 (TR4) and TR2 regulates TRAIL-induced apoptosis.

Journal Article Proc Natl Acad Sci U S A · December 13, 2005 Tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) is a cytokine with potential therapeutic value against cancers because of its selective cytotoxicity to many transformed, but not normal, cells. The "decoy receptors" TRAIL-R3 (TR3) and ... Full text Link to item Cite

Amelioration of inflammatory arthritis by targeting the pre-ligand assembly domain of tumor necrosis factor receptors.

Journal Article Nat Med · October 2005 Tumor necrosis factor (TNF)-alpha has an important role in the pathogenesis of autoimmune and inflammatory diseases such as rheumatoid and septic arthritis. The biological effects of TNF-alpha are mediated by binding to TNF receptors TNFR1 (also known as P ... Full text Link to item Cite

TNF, cell death and inflammation

Journal Article Current Medicinal Chemistry: Anti-Inflammatory and Anti-Allergy Agents · January 1, 2005 Tumor necrosis factor (TNFα) is a pleiotropic cytokine that mediates diverse biological responses. In the immune system, TNFα facilitates many aspects of immune responses against pathogenic challenges. While TNFα plays a critical role in the immune defense ... Full text Cite

Editorial

Journal Article Current Medicinal Chemistry: Anti-Inflammatory and Anti-Allergy Agents · January 1, 2005 Full text Cite

Flow cytometric analysis of fluorescence resonance energy transfer: a tool for high-throughput screening of molecular interactions in living cells.

Journal Article Methods Mol Biol · 2004 The study of cellular processes has been facilitated by the use of methods to detect molecular associations both in vivo and in vitro. An invaluable tool to study molecular associations associated with dynamic processes in living cells utilizes the phenome ... Full text Link to item Cite

Monitoring molecular interactions in living cells using flow cytometric analysis of fluorescence resonance energy transfer.

Journal Article Methods Mol Biol · 2004 Variants of the green fluorescence protein (GFP) are useful tools in many biological research applications. Two of the GFP spectral variants, the cyan and yellow fluorescence proteins (CFP and YFP), have compatible excitation and emission properties as flu ... Full text Link to item Cite

A role for tumor necrosis factor receptor-2 and receptor-interacting protein in programmed necrosis and antiviral responses.

Journal Article J Biol Chem · December 19, 2003 Featured Publication Members of the tumor necrosis factor (TNF) receptor (TNFR) superfamily are potent regulators of apoptosis, a process that is important for the maintenance of immune homeostasis. Recent evidence suggests that TNFR-1 and Fas and TRAIL receptors can also trig ... Full text Link to item Cite

Tumor Necrosis Factor Family Ligands and Receptors in the Immune System: Targets for Future Pharmaceuticals.

Journal Article Drug News Perspect · October 2002 Members of the superfamily of ligands related to tumor necrosis factor (TNF) as well as the superfamily of receptors that recognize these ligands play critical roles in various aspects of mammalian lymphocyte development and immune function. Many of the re ... Full text Link to item Cite

Fluorescence resonance energy transfer analysis of cell surface receptor interactions and signaling using spectral variants of the green fluorescent protein.

Journal Article Cytometry · August 1, 2001 BACKGROUND: Fluorescence resonance energy transfer (FRET) is a powerful technique for measuring molecular interactions at Angstrom distances. We present a new method for FRET that utilizes the unique spectral properties of variants of the green fluorescent ... Full text Link to item Cite

The multifaceted role of Fas signaling in immune cell homeostasis and autoimmunity.

Journal Article Nat Immunol · December 2000 Originally identified as a cell surface receptor that triggered the death of lymphocytes and tumor cells, it is now recognized that Fas (also known as CD95 or Apo-I) has distinct functions in the life and death of different cell types in the immune system. ... Full text Link to item Cite

The pre-ligand binding assembly domain: a potential target of inhibition of tumour necrosis factor receptor function.

Journal Article Ann Rheum Dis · November 2000 Signalling by the tumour necrosis factor receptors (TNFR) is thought to be mediated by the binding of the trimeric ligand TNF to three monomeric subunits of the receptor. This ligand induced trimerisation model of TNFR signalling is mainly supported by cry ... Full text Link to item Cite

Fas preassociation required for apoptosis signaling and dominant inhibition by pathogenic mutations.

Journal Article Science · June 30, 2000 Heterozygous mutations encoding abnormal forms of the death receptor Fas dominantly interfere with Fas-induced lymphocyte apoptosis in human autoimmune lymphoproliferative syndrome. This effect, rather than depending on ligand-induced receptor oligomerizat ... Full text Link to item Cite

A domain in TNF receptors that mediates ligand-independent receptor assembly and signaling.

Journal Article Science · June 30, 2000 Featured Publication A conserved domain in the extracellular region of the 60- and 80-kilodalton tumor necrosis factor receptors (TNFRs) was identified that mediates specific ligand-independent assembly of receptor trimers. This pre-ligand-binding assembly domain (PLAD) is phy ... Full text Link to item Cite

Measurement of molecular interactions in living cells by fluorescence resonance energy transfer between variants of the green fluorescent protein.

Journal Article Sci STKE · June 27, 2000 Many signal transduction pathways operate through oligomerization of proteins into multi-subunit complexes. Although biochemical assays can identify potential protein-protein interactions, studying these interactions in living cells is more challenging. Fl ... Full text Link to item Cite

A crucial role for p80 TNF-R2 in amplifying p60 TNF-R1 apoptosis signals in T lymphocytes.

Journal Article Eur J Immunol · February 2000 Tumor necrosis factor-alpha (TNF-alpha) can elicit many cellular responses including programmed cell death or apotosis. TNF-alpha-induced apoptosis has been largely attributed to the p60 TNF-R1 receptor. The role of p80 in TNF-alpha-mediated apoptosis is l ... Full text Link to item Cite

Inherited human Caspase 10 mutations underlie defective lymphocyte and dendritic cell apoptosis in autoimmune lymphoproliferative syndrome type II.

Journal Article Cell · July 9, 1999 Featured Publication Caspases are cysteine proteases that mediate programmed cell death in phylogenetically diverse multicellular organisms. We report here two kindreds with autoimmune lymphoproliferative syndrome (ALPS) type II, characterized by abnormal lymphocyte and dendri ... Full text Link to item Cite

CTLA-4-Mediated inhibition of early events of T cell proliferation.

Journal Article J Immunol · May 15, 1999 CTLA-4 engagement by mAbs inhibits, while CD28 enhances, IL-2 production and proliferation upon T cell activation. Here, we have analyzed the mechanisms involved in CTLA-4-mediated inhibition of T cell activation of naive CD4+ T cells using Ab cross-linkin ... Link to item Cite

Mature T lymphocyte apoptosis--immune regulation in a dynamic and unpredictable antigenic environment.

Journal Article Annu Rev Immunol · 1999 Apoptosis of mature T lymphocytes preserves peripheral homeostasis and tolerance by countering the profound changes in the number and types of T cells stimulated by diverse antigens. T cell apoptosis occurs in at least two major forms: antigen-driven and l ... Full text Link to item Cite

Thymic expression of the transcription factor Nur77 rescues the T cell but not the B cell abnormality of gld/gld mice.

Journal Article J Immunol · October 15, 1998 Fas and Fas ligand are critical regulators of lymphocyte homeostasis. Disruption of this pathway in the spontaneous mouse mutant gld leads to autoimmunity characterized by the appearance of a population of CD4- 8- B220+ T cells and the production of autoan ... Link to item Cite

Functional redundancy of the Nur77 and Nor-1 orphan steroid receptors in T-cell apoptosis.

Journal Article EMBO J · April 15, 1997 The transcription factor Nur77 (NGFI-B), a member of the steroid nuclear receptor superfamily, is induced to a high level during T-cell receptor (TCR)-mediated apoptosis. A transgenic dominant-negative Nur77 protein can inhibit the apoptotic process accomp ... Full text Link to item Cite

NMR structural characterization of the CDK inhibitor p19INK4d.

Journal Article FEBS Lett · January 20, 1997 p19INK4d is a 165 amino acid protein that belongs to the INK4 family of CDK4 and CDK6 inhibitors. Assignments of 1H, 15N and 13C resonances have enabled the determination of the secondary structure of the protein which is largely alpha-helical (residues 14 ... Full text Link to item Cite

A role for the orphan steroid receptor Nur77 in apoptosis accompanying antigen-induced negative selection.

Journal Article Immunity · September 1995 The transcription factor Nur77, an orphan member of the nuclear hormone receptor superfamily, is highly expressed during T cell receptor-signaled apoptosis, suggesting a possible role for Nur77 in negative selection. We examined this by generating two sets ... Full text Link to item Cite

Identification of human and mouse p19, a novel CDK4 and CDK6 inhibitor with homology to p16ink4.

Journal Article Mol Cell Biol · May 1995 The cell cycle in mammalian cells is regulated by a series of cyclins and cyclin-dependent kinases (CDKs). The G1/S checkpoint is mainly dictated by the kinase activities of the cyclin D-CDK4 and/or cyclin D-CDK6 complex and the cyclin E-CDK2 complex. Thes ... Full text Link to item Cite

A role for the cytoplasmic tail of the beta chain of CD8 in thymic selection.

Journal Article Immunity · July 1994 The CD8 coreceptor plays a critical role in the recognition of foreign antigens by mature T cells and in the development of class I-restricted T cells. CD8 can be expressed on the surface of T cells as either a heterodimer composed of an alpha and beta cha ... Full text Link to item Cite