Maria Elena Cardenas-Corona

Journal article Cell Host Microbe · October 9, 2019 Calcium is an abundant intracellular ion, and calcium homeostasis plays crucial roles in several cellular processes. The calcineurin signaling cascade is one of the major pathways governed by intracellular calcium. Calcineurin, a conserved protein from yea ... Full text Link to item Cite

Pbp1-Interacting Protein Mkt1 Regulates Virulence and Sexual Reproduction in Cryptococcus neoformans.

Journal article Front Cell Infect Microbiol · 2019 The Mkt1-Pbp1 complex promotes mating-type switching by regulating the translation of HO mRNA in Saccharomyces cerevisiae. Here, we performed in vivo immunoprecipitation assays and mass spectrometry analyses in the human fungal pathogen Cryptococcus neofor ... Full text Open Access Link to item Cite

Had1 Is Required for Cell Wall Integrity and Fungal Virulence in Cryptococcus neoformans.

Journal article G3 (Bethesda) · February 2, 2018 Calcineurin modulates environmental stress survival and virulence of the human fungal pathogen Cryptococcus neoformans Previously, we identified 44 putative calcineurin substrates, and proposed that the calcineurin pathway is branched to regulate targets i ... Full text Link to item Cite

Dissecting the Roles of the Calcineurin Pathway in Unisexual Reproduction, Stress Responses, and Virulence in Cryptococcus deneoformans.

Journal article Genetics · February 2018 The Ca2+/calmodulin-dependent protein phosphatase calcineurin orchestrates sexual reproduction, stress responses, and virulence via branched downstream pathways in the opportunistic human fungal pathogen Cryptococcus neoformans The calcineurin-binding prot ... Full text Link to item Cite

Mon1 Is Essential for Fungal Virulence and Stress Survival in Cryptococcus neoformans.

Journal article Mycobiology · 2018 Mon1 is a guanine nucleotide exchange factor subunit that activates the Ypt7 Rab GTPase and is essential for vacuole trafficking and autophagy in eukaryotic organisms. Here, we identified and characterized the function of Mon1, an ortholog of Saccharomyces ... Full text Link to item Cite

Phosphate is the third nutrient monitored by TOR in Candida albicans and provides a target for fungal-specific indirect TOR inhibition.

Journal article Proc Natl Acad Sci U S A · June 13, 2017 The Target of Rapamycin (TOR) pathway regulates morphogenesis and responses to host cells in the fungal pathogen Candida albicans Eukaryotic Target of Rapamycin complex 1 (TORC1) induces growth and proliferation in response to nitrogen and carbon source av ... Full text Link to item Cite

Elucidation of the calcineurin-Crz1 stress response transcriptional network in the human fungal pathogen Cryptococcus neoformans.

Journal article PLoS Genet · April 2017 Calcineurin is a highly conserved Ca2+/calmodulin-dependent serine/threonine-specific protein phosphatase that orchestrates cellular Ca2+ signaling responses. In Cryptococcus neoformans, calcineurin is activated by multiple stresses including high temperat ... Full text Link to item Cite

A non-canonical RNA degradation pathway suppresses RNAi-dependent epimutations in the human fungal pathogen Mucor circinelloides.

Journal article PLoS Genet · March 2017 Mucorales are a group of basal fungi that includes the casual agents of the human emerging disease mucormycosis. Recent studies revealed that these pathogens activate an RNAi-based pathway to rapidly generate drug-resistant epimutant strains when exposed t ... Full text Link to item Cite

Calcineurin Targets Involved in Stress Survival and Fungal Virulence.

Journal article PLoS Pathog · September 2016 Calcineurin governs stress survival, sexual differentiation, and virulence of the human fungal pathogen Cryptococcus neoformans. Calcineurin is activated by increased Ca2+ levels caused by stress, and transduces signals by dephosphorylating protein substra ... Full text Open Access Link to item Cite

Cancer-associated isocitrate dehydrogenase mutations induce mitochondrial DNA instability.

Journal article Hum Mol Genet · August 15, 2016 A major advance in understanding the progression and prognostic outcome of certain cancers, such as low-grade gliomas, acute myeloid leukaemia, and chondrosarcomas, has been the identification of early-occurring mutations in the NADP+-dependent isocitrate ... Full text Link to item Cite

Vesicular Trafficking Systems Impact TORC1-Controlled Transcriptional Programs in Saccharomyces cerevisiae.

Journal article G3 (Bethesda) · January 6, 2016 The Target of Rapamycin Complex I (TORC1) orchestrates global reprogramming of transcriptional programs in response to myriad environmental conditions, yet, despite the commonality of the TORC1 complex components, different TORC1-inhibitory conditions do n ... Full text Link to item Cite

Branched-Chain Aminotransferases Control TORC1 Signaling in Saccharomyces cerevisiae.

Journal article PLoS Genet · December 2015 The conserved target of rapamycin complex 1 (TORC1) integrates nutrient signals to orchestrate cell growth and proliferation. Leucine availability is conveyed to control TORC1 activity via the leu-tRNA synthetase/EGOC-GTPase module in yeast and mammals, bu ... Full text Link to item Cite

L-leucine partially rescues translational and developmental defects associated with zebrafish models of Cornelia de Lange syndrome.

Journal article Hum Mol Genet · March 15, 2015 Cohesinopathies are human genetic disorders that include Cornelia de Lange syndrome (CdLS) and Roberts syndrome (RBS) and are characterized by defects in limb and craniofacial development as well as mental retardation. The developmental phenotypes of CdLS ... Full text Link to item Cite

Antifungal drug resistance evoked via RNAi-dependent epimutations.

Journal article Nature · September 25, 2014 Microorganisms evolve via a range of mechanisms that may include or involve sexual/parasexual reproduction, mutators, aneuploidy, Hsp90 and even prions. Mechanisms that may seem detrimental can be repurposed to generate diversity. Here we show that the hum ... Full text Link to item Cite

Endolysosomal membrane trafficking complexes drive nutrient-dependent TORC1 signaling to control cell growth in Saccharomyces cerevisiae.

Journal article Genetics · April 2014 The rapamycin-sensitive and endomembrane-associated TORC1 pathway controls cell growth in response to nutrients in eukaryotes. Mutations in class C Vps (Vps-C) complexes are synthetically lethal with tor1 mutations and confer rapamycin hypersensitivity in ... Full text Link to item Cite

Estrogen receptor antagonists are anti-cryptococcal agents that directly bind EF hand proteins and synergize with fluconazole in vivo.

Journal article mBio · February 11, 2014 UNLABELLED: Cryptococcosis is an infectious disease of global significance for which new therapies are needed. Repurposing previously developed drugs for new indications can expedite the translation of new therapies from bench to beside. Here, we character ... Full text Link to item Cite

Genomic insights into the atopic eczema-associated skin commensal yeast Malassezia sympodialis.

Journal article mBio · January 22, 2013 UNLABELLED: Malassezia commensal yeasts are associated with a number of skin disorders, such as atopic eczema/dermatitis and dandruff, and they also can cause systemic infections. Here we describe the 7.67-Mbp genome of Malassezia sympodialis, a species as ... Full text Link to item Cite

Genomic insights into the atopic eczema-associated skin commensal yeast Malassezia sympodialis.

Journal article mBio · 2013 ABSTRACT: Malassezia commensal yeasts are associated with a number of skin disorders, such as atopic eczema/dermatitis and dandruff, and they also can cause systemic infections. Here we describe the 7.67-Mbp genome of Malassezia sympodialis, a species asso ... Full text Cite

Rapamycin exerts antifungal activity in vitro and in vivo against Mucor circinelloides via FKBP12-dependent inhibition of Tor.

Journal article Eukaryot Cell · March 2012 The zygomycete Mucor circinelloides is an opportunistic fungal pathogen that commonly infects patients with malignancies, diabetes mellitus, and solid organ transplants. Despite the widespread use of antifungal therapy in the management of zygomycosis, the ... Full text Link to item Cite

Calcineurin colocalizes with P-bodies and stress granules during thermal stress in Cryptococcus neoformans.

Journal article Eukaryot Cell · November 2011 Calcineurin is a calcium-calmodulin-activated serine/threonine-specific phosphatase that operates during cellular responses to stress and plays a prominent role in transcriptional control, whereas regulatory events beyond transcription are less well charac ... Full text Link to item Cite

Exploiting and subverting Tor signaling in the pathogenesis of fungi, parasites, and viruses.

Journal article PLoS Pathog · September 2011 Full text Link to item Cite

Association of calcineurin with the COPI protein Sec28 and the COPII protein Sec13 revealed by quantitative proteomics.

Journal article PLoS One · 2011 Calcineurin is a calcium-calmodulin-dependent serine/threonine specific protein phosphatase operating in key cellular processes governing responses to extracellular cues. Calcineurin is essential for growth at high temperature and virulence of the human fu ... Full text Link to item Cite

On the Roles of Calcineurin in Fungal Growth and Pathogenesis.

Journal article Curr Fungal Infect Rep · December 2010 Calcineurin is a calcium-activated phosphatase that controls morphogenesis and stress responses in eukaryotes. Fungal pathogens have adopted the calcineurin pathway to survive and effectively propagate within the host. The difficulty in treating fungal inf ... Full text Link to item Cite

Conservation, duplication, and loss of the Tor signaling pathway in the fungal kingdom.

Journal article BMC Genomics · September 23, 2010 BACKGROUND: The nutrient-sensing Tor pathway governs cell growth and is conserved in nearly all eukaryotic organisms from unicellular yeasts to multicellular organisms, including humans. Tor is the target of the immunosuppressive drug rapamycin, which in c ... Full text Open Access Link to item Cite

TORC1 signaling in the budding yeast endomembrane system and control of cell-cell adhesion in pathogenic fungi

Journal article · January 1, 2010 The rapamycin-sensitive TORC1 protein kinase is the central component of a conserved signal transduction cascade controlling cell growth in response to nutrients and growth factors. Groundbreaking studies are uncovering novel roles for the endomembrane ves ... Full text Cite

Human protein phosphatase PP6 regulatory subunits provide Sit4-dependent and rapamycin-sensitive sap function in Saccharomyces cerevisiae.

Journal article PLoS One · July 21, 2009 In the budding yeast Saccharomyces cerevisiae the protein phosphatase Sit4 and four associated proteins (Sap4, Sap155, Sap185, and Sap190) mediate G(1) to S cell cycle progression and a number of signaling events controlled by the target of rapamycin TOR s ... Full text Link to item Cite

The protein kinase Tor1 regulates adhesin gene expression in Candida albicans.

Journal article PLoS Pathog · February 2009 Eukaryotic cell growth is coordinated in response to nutrient availability, growth factors, and environmental stimuli, enabling cell-cell interactions that promote survival. The rapamycin-sensitive Tor1 protein kinase, which is conserved from yeasts to hum ... Full text Link to item Cite

Signaling cascades as drug targets in model and pathogenic fungi.

Journal article Curr Opin Investig Drugs · August 2008 Microbes evolved to produce natural products that inhibit growth of competing soil microorganisms. In many cases these compounds act on fungi, which are eukaryotes with conserved gene sequences closely related to metazoans, including humans. The calcineuri ... Link to item Cite

A Mep2-dependent transcriptional profile links permease function to gene expression during pseudohyphal growth in Saccharomyces cerevisiae.

Journal article Mol Biol Cell · July 2008 The ammonium permease Mep2 is required for the induction of pseudohyphal growth, a process in Saccharomyces cerevisiae that occurs in response to nutrient limitation. Mep2 has both a transport and a regulatory function, supporting models in which Mep2 acts ... Full text Link to item Cite

Nuclear translocation of Gln3 in response to nutrient signals requires Golgi-to-endosome trafficking in Saccharomyces cerevisiae.

Journal article Proc Natl Acad Sci U S A · May 20, 2008 The yeast Saccharomyces cerevisiae has developed specialized mechanisms that enable growth on suboptimal nitrogen sources. Exposure of yeast cells to poor nitrogen sources or treatment with the Tor kinase inhibitor rapamycin elicits activation of Gln3 and ... Full text Link to item Cite

Nutritional control via Tor signaling in Saccharomyces cerevisiae.

Journal article Curr Opin Microbiol · April 2008 The yeast Saccharomyces cerevisiae senses and responds to nutrients by adapting its growth rate and undergoing morphogenic transitions to ensure survival. The Tor pathway is a major integrator of nutrient-derived signals that in coordination with other sig ... Full text Link to item Cite

Yeast as a model to study the immunosuppressive and chemotherapeutic drug rapamycin

Journal article · December 1, 2007 Rapamycin is a natural product of a soil bacterium and has potent immunosuppressive, and antiproliferative actions. First identified in 1975 as an antifungal drug, rapamycin languished in obscurity after it was found to cause bone marrow suppression [112]. ... Full text Cite

Efficient Tor signaling requires a functional class C Vps protein complex in Saccharomyces cerevisiae.

Journal article Genetics · August 2007 The Tor kinases regulate responses to nutrients and control cell growth. Unlike most organisms that only contain one Tor protein, Saccharomyces cerevisiae expresses two, Tor1 and Tor2, which are thought to share all of the rapamycin-sensitive functions att ... Full text Link to item Cite

Sensing the environment: lessons from fungi.

Journal article Nat Rev Microbiol · January 2007 All living organisms use numerous signal-transduction systems to sense and respond to their environments and thereby survive and proliferate in a range of biological niches. Molecular dissection of these signalling networks has increased our understanding ... Full text Link to item Cite

Tor and cyclic AMP-protein kinase A: two parallel pathways regulating expression of genes required for cell growth.

Journal article Eukaryot Cell · January 2005 In the budding yeast Saccharomyces cerevisiae, the Tor and cyclic AMP-protein kinase A (cAMP-PKA) signaling cascades respond to nutrients and regulate coordinately the expression of genes required for cell growth, including ribosomal protein (RP) and stres ... Full text Link to item Cite

TOR controls transcriptional and translational programs via Sap-Sit4 protein phosphatase signaling effectors.

Journal article Mol Cell Biol · October 2004 The Tor kinases are the targets of the immunosuppressive drug rapamycin and couple nutrient availability to cell growth. In the budding yeast Saccharomyces cerevisiae, the PP2A-related phosphatase Sit4 together with its regulatory subunit Tap42 mediates se ... Full text Link to item Cite

Nutrient signaling through TOR kinases controls gene expression and cellular differentiation in fungi.

Journal article Curr Top Microbiol Immunol · 2004 The TOR kinases were first identified in Saccharomyces cerevisiae as the targets of the immunosuppressive drug rapamycin. Subsequent studies employing rapamycin as a tool in yeast have given us insight into the structure and function of the TOR kinases, as ... Full text Link to item Cite

The tor pathway regulates gene expression by linking nutrient sensing to histone acetylation.

Journal article Mol Cell Biol · January 2003 The Tor pathway mediates cell growth in response to nutrient availability, in part by inducing ribosomal protein (RP) gene expression via an unknown mechanism. Expression of RP genes coincides with recruitment of the Esa1 histone acetylase to RP gene promo ... Full text Link to item Cite

Mating-type-specific and nonspecific PAK kinases play shared and divergent roles in Cryptococcus neoformans.

Journal article Eukaryot Cell · April 2002 Cryptococcus neoformans is an opportunistic fungal pathogen with a defined sexual cycle involving fusion of haploid MATalpha and MATa cells. Virulence has been linked to the mating type, and MATalpha cells are more virulent than congenic MATa cells. To stu ... Full text Link to item Cite

Calcineurin is essential for survival during membrane stress in Candida albicans.

Journal article EMBO J · February 15, 2002 The immunosuppressants cyclosporin A (CsA) and FK506 inhibit the protein phosphatase calcineurin and block T-cell activation and transplant rejection. Calcineurin is conserved in microorganisms and plays a general role in stress survival. CsA and FK506 are ... Full text Link to item Cite

The TOR signal transduction cascade controls cellular differentiation in response to nutrients.

Journal article Mol Biol Cell · December 2001 Rapamycin binds and inhibits the Tor protein kinases, which function in a nutrient-sensing signal transduction pathway that has been conserved from the yeast Saccharomyces cerevisiae to humans. In yeast cells, the Tor pathway has been implicated in regulat ... Full text Link to item Cite

Rapamycin and less immunosuppressive analogs are toxic to Candida albicans and Cryptococcus neoformans via FKBP12-dependent inhibition of TOR.

Journal article Antimicrob Agents Chemother · November 2001 Candida albicans and Cryptococcus neoformans cause both superficial and disseminated infections in humans. Current antifungal therapies for deep-seated infections are limited to amphotericin B, flucytosine, and azoles. A limitation is that commonly used az ... Full text Link to item Cite

Two cyclophilin A homologs with shared and distinct functions important for growth and virulence of Cryptococcus neoformans.

Journal article EMBO Rep · June 2001 Cyclophilin A is the target of the immunosuppressant cyclosporin A (CsA) and is encoded by a single unique gene conserved from yeast to humans. In the pathogenic fungus Cryptococcus neoformans, two homologous linked genes, CPA1 and CPA2, were found to enco ... Full text Link to item Cite

The TOR kinases link nutrient sensing to cell growth.

Journal article J Biol Chem · March 30, 2001 Rapamycin is an immunosuppressive natural product that inhibits the proliferation of T-cells in response to nutrients and growth factors. Rapamycin binds to the peptidyl-prolyl isomerase FKBP12 and forms protein-drug complexes that inhibit signal transduct ... Full text Link to item Cite

Calcineurin regulatory subunit is essential for virulence and mediates interactions with FKBP12-FK506 in Cryptococcus neoformans.

Journal article Mol Microbiol · February 2001 Calcineurin is a Ca2+-calmodulin-regulated protein phosphatase that is the target of the immunosuppressive drugs cyclosporin A and FK506. Calcineurin is a heterodimer composed of a catalytic A and a regulatory B subunit. In previous studies, the calcineuri ... Full text Link to item Cite

The Ess1 prolyl isomerase is linked to chromatin remodeling complexes and the general transcription machinery.

Journal article EMBO J · July 17, 2000 The Ess1/Pin1 peptidyl-prolyl isomerase (PPIase) is thought to control mitosis by binding to cell cycle regulatory proteins and altering their activity. Here we isolate temperature-sensitive ess1 mutants and identify six multicopy suppressors that rescue t ... Full text Link to item Cite

Cyclophilin A and Ess1 interact with and regulate silencing by the Sin3-Rpd3 histone deacetylase.

Journal article EMBO J · July 17, 2000 Three families of prolyl isomerases have been identified: cyclophilins, FK506-binding proteins (FKBPs) and parvulins. All 12 cyclophilins and FKBPs are dispensable for growth in yeast, whereas the one parvulin homolog, Ess1, is essential. We report here th ... Full text Link to item Cite

Synergistic antifungal activities of bafilomycin A(1), fluconazole, and the pneumocandin MK-0991/caspofungin acetate (L-743,873) with calcineurin inhibitors FK506 and L-685,818 against Cryptococcus neoformans.

Journal article Antimicrob Agents Chemother · March 2000 Cryptococcus neoformans is an opportunistic fungal pathogen that causes life-threatening infections of the central nervous system. Existing therapies include amphotericin B, fluconazole, and flucytosine, which are limited by toxic side effects and the emer ... Full text Link to item Cite

The G protein-coupled receptor gpr1 is a nutrient sensor that regulates pseudohyphal differentiation in Saccharomyces cerevisiae.

Journal article Genetics · February 2000 Pseudohyphal differentiation in the budding yeast Saccharomyces cerevisiae is induced in diploid cells in response to nitrogen starvation and abundant fermentable carbon source. Filamentous growth requires at least two signaling pathways: the pheromone res ... Full text Link to item Cite

Immunosuppressive and nonimmunosuppressive cyclosporine analogs are toxic to the opportunistic fungal pathogen Cryptococcus neoformans via cyclophilin-dependent inhibition of calcineurin.

Journal article Antimicrob Agents Chemother · January 2000 Cyclosporine (CsA) is an immunosuppressive and antimicrobial drug which, in complex with cyclophilin A, inhibits the protein phosphatase calcineurin. We recently found that Cryptococcus neoformans growth is resistant to CsA at 24 degrees C but sensitive at ... Full text Link to item Cite

The TOR signaling cascade regulates gene expression in response to nutrients.

Journal article Genes Dev · December 15, 1999 Rapamycin inhibits the TOR kinases, which regulate cell proliferation and mRNA translation and are conserved from yeast to man. The TOR kinases also regulate responses to nutrients, including sporulation, autophagy, mating, and ribosome biogenesis. We have ... Full text Link to item Cite

Antifungal activities of antineoplastic agents: Saccharomyces cerevisiae as a model system to study drug action.

Journal article Clin Microbiol Rev · October 1999 Recent evolutionary studies reveal that microorganisms including yeasts and fungi are more closely related to mammals than was previously appreciated. Possibly as a consequence, many natural-product toxins that have antimicrobial activity are also toxic to ... Full text Link to item Cite

TOR kinase homologs function in a signal transduction pathway that is conserved from yeast to mammals.

Journal article Mol Cell Endocrinol · September 10, 1999 Rapamycin is a natural product with potent antifungal and immunosuppressive activities. Rapamycin binds to the FKBP12 prolyl isomerase, and the resulting protein-drug complex inhibits the TOR kinase homologs. Both the FKBP12 and the TOR proteins are highly ... Full text Link to item Cite

Secretion of FK506/FK520 and rapamycin by Streptomyces inhibits the growth of competing Saccharomyces cerevisiae and Cryptococcus neoformans.

Journal article Microbiology (Reading) · August 1999 FK506 and rapamycin are immunosuppressants that inhibit signalling cascades required for T-cell activation, yet both are natural products of Streptomyces that live in the soil. FK506 and rapamycin also have potent antimicrobial activity against yeast and p ... Full text Link to item Cite

Protein kinase activity and identification of a toxic effector domain of the target of rapamycin TOR proteins in yeast.

Journal article Mol Biol Cell · August 1999 In complex with FKBP12, the immunosuppressant rapamycin binds to and inhibits the yeast TOR1 and TOR2 proteins and the mammalian homologue mTOR/FRAP/RAFT1. The TOR proteins promote cell cycle progression in yeast and human cells by regulating translation a ... Full text Link to item Cite

Rapamycin antifungal action is mediated via conserved complexes with FKBP12 and TOR kinase homologs in Cryptococcus neoformans.

Journal article Mol Cell Biol · June 1999 Cryptococcus neoformans is a fungal pathogen that causes meningitis in patients immunocompromised by AIDS, chemotherapy, organ transplantation, or high-dose steroids. Current antifungal drug therapies are limited and suffer from toxic side effects and drug ... Full text Link to item Cite

CNS1 encodes an essential p60/Sti1 homolog in Saccharomyces cerevisiae that suppresses cyclophilin 40 mutations and interacts with Hsp90.

Journal article Mol Cell Biol · December 1998 Cyclophilins are cis-trans-peptidyl-prolyl isomerases that bind to and are inhibited by the immunosuppressant cyclosporin A (CsA). The toxic effects of CsA are mediated by the 18-kDa cyclophilin A protein. A larger cyclophilin of 40 kDa, cyclophilin 40, is ... Full text Link to item Cite

Signal-transduction cascades as targets for therapeutic intervention by natural products.

Journal article Trends Biotechnol · October 1998 Many bacteria and fungi produce natural products that are toxic to other microorganisms and have a variety of physiological effects in animals. Recent studies have revealed that, in several cases, the targets of these agents are components of conserved sig ... Full text Link to item Cite

Expression, enzyme activity, and subcellular localization of mammalian target of rapamycin in insulin-responsive cells.

Journal article Biochem Biophys Res Commun · December 29, 1997 The role of the mammalian target of rapamycin (mTOR) was investigated in insulin responsive cell lines. mTOR was expressed at high levels in insulin responsive cell types and in 3T3-L1 cells mTOR expression levels increased dramatically as cells differenti ... Full text Link to item Cite

All cyclophilins and FK506 binding proteins are, individually and collectively, dispensable for viability in Saccharomyces cerevisiae.

Journal article Proc Natl Acad Sci U S A · November 25, 1997 The cyclophilins and FK506 binding proteins (FKBPs) bind to cyclosporin A, FK506, and rapamycin and mediate their immunosuppressive and toxic effects, but the physiological functions of these proteins are largely unknown. Cyclophilins and FKBPs are ubiquit ... Full text Link to item Cite

Functions of FKBP12 and mitochondrial cyclophilin active site residues in vitro and in vivo in Saccharomyces cerevisiae.

Journal article Mol Biol Cell · November 1997 Cyclophilin and FK506 binding protein (FKBP) accelerate cis-trans peptidyl-prolyl isomerization and bind to and mediate the effects of the immunosuppressants cyclosporin A and FK506. The normal cellular functions of these proteins, however, are unknown. We ... Full text Link to item Cite

STT4 is an essential phosphatidylinositol 4-kinase that is a target of wortmannin in Saccharomyces cerevisiae.

Journal article J Biol Chem · October 31, 1997 Wortmannin is a natural product that inhibits signal transduction. One target of wortmannin in mammalian cells is the 110-kDa catalytic subunit of phosphatidylinositol 3-kinase (PI 3-kinase). We show that wortmannin is toxic to the yeast Saccharomyces cere ... Full text Link to item Cite

Calcineurin mutants render T lymphocytes resistant to cyclosporin A.

Journal article Mol Pharmacol · September 1996 The immunosuppressants cyclosporin A (CsA) and FK506 have been widely used to prevent and treat graft rejection after human organ and tissue transplantations. CsA and FK506 associate with intracellular binding proteins (i.e., CsA with cyclophilin A and FK5 ... Link to item Cite

Mammalian RAFT1 kinase domain provides rapamycin-sensitive TOR function in yeast.

Journal article Genes Dev · February 1, 1996 In complex with the prolyl isomerase FKBP12, the natural product rapamycin blocks signal transduction in organisms as diverse as yeast and man. The yeast targets of FKBP12-rapamycin, TOR1 and TOR2, are large proteins with homology to lipid and protein kina ... Full text Link to item Cite

FKBP12-rapamycin target TOR2 is a vacuolar protein with an associated phosphatidylinositol-4 kinase activity.

Journal article EMBO J · December 1, 1995 In complex with the immunophilin FKBP12, the natural product rapamycin inhibits signal transduction events required for G1 to S phase cell cycle progression in yeast and mammalian cells. Genetic studies in yeast first implicated the TOR1 and TOR2 proteins ... Full text Link to item Cite

Molecular mechanisms of immunosuppression by cyclosporine, FK506, and rapamycin.

Journal article Curr Opin Nephrol Hypertens · November 1995 The immunosuppressant cyclosporine A revolutionized treatment of graft rejection. Two newer agents, FK506 and rapamycin, show great clinical potential. These drugs suppress the immune system by forming protein-drug complexes that interact with and inhibit ... Full text Link to item Cite

vph6 mutants of Saccharomyces cerevisiae require calcineurin for growth and are defective in vacuolar H(+)-ATPase assembly.

Journal article Genetics · November 1995 We have characterized a Saccharomyces cerevisiae mutant strain that is hypersensitive to cyclosporin A (CsA) and FK506, immunosuppressants that inhibit calcineurin, a serine-threonine-specific phosphatase (PP2B). A single nuclear mutation, designated cev1 ... Full text Link to item Cite

Myristoylation of calcineurin B is not required for function or interaction with immunophilin-immunosuppressant complexes in the yeast Saccharomyces cerevisiae.

Journal article J Biol Chem · October 20, 1995 Calcineurin is a heterodimeric Ca2+/calmodulin-dependent protein phosphatase that regulates signal transduction and is the target of immunophilin-immunosuppressive drug complexes in T-lymphocytes and in yeast. Calcineurin is composed of a catalytic A subun ... Full text Link to item Cite

Mutations that perturb cyclophilin A ligand binding pocket confer cyclosporin A resistance in Saccharomyces cerevisiae.

Journal article J Biol Chem · September 8, 1995 In complex with the peptidyl-prolyl isomerase cyclophilin A, the immunosuppressive antifungal drug cyclosporin A (CsA) inhibits a Ca2+/calmodulin-dependent protein phosphatase, calcineurin, which regulates signal transduction. We isolated and characterized ... Full text Link to item Cite

Targets of immunophilin-immunosuppressant complexes are distinct highly conserved regions of calcineurin A.

Journal article EMBO J · June 15, 1995 The immunosuppressive complexes cyclophilin A-cyclosporin A (CsA) and FKBP12-FK506 inhibit calcineurin, a heterodimeric Ca(2+)-calmodulin-dependent protein phosphatase that regulates signal transduction. We have characterized CsA- or FK506-resistant mutant ... Full text Link to item Cite

Role of calcium in T-lymphocyte activation.

Journal article Adv Second Messenger Phosphoprotein Res · 1995 Full text Link to item Cite

Immunophilins interact with calcineurin in the absence of exogenous immunosuppressive ligands.

Journal article EMBO J · December 15, 1994 The peptidyl-prolyl isomerases FKBP12 and cyclophilin A (immunophilins) form complexes with the immunosuppressants FK506 and cyclosporin A that inhibit the phosphatase calcineurin. With the yeast two hybrid system, we detect complexes between FKBP12 and th ... Full text Link to item Cite

Antifungal effects of cyclosporine and FK 506 are mediated via immunophilin-dependent calcineurin inhibition.

Journal article Transplant Proc · October 1994 Link to item Cite

Yeast as model T cells

Journal article Perspectives in Drug Discovery and Design · August 1, 1994 The immunosuppressants cyclosporin A, FK-506, and rapamycin prevent T-cell activation by inhibiting intermediate signal transduction steps. Studies have focused on their mechanisms of action, with the aim of both designing novel immunosuppressants and unde ... Full text Cite

Calcineurin is essential in cyclosporin A- and FK506-sensitive yeast strains.

Journal article Proc Natl Acad Sci U S A · June 7, 1994 The immunophilin-immunosuppressant complexes cyclophilin-cyclosporin A (CsA) and FKBP12-FK506 inhibit the phosphatase calcineurin to block T-cell activation. Although cyclophilin A, FKBP12, and calcineurin are highly conserved from yeast to man, none had p ... Full text Link to item Cite

The regulation of DNA topoisomerase II by casein kinase II.

Journal article Cell Mol Biol Res · 1994 DNA topoisomerase II is an essential nuclear enzyme required for the proper condensation and segregation of chromosomes during mitotic and meiotic cell division. The enzyme exists in the cell as a phosphoprotein, and it is most highly phosphorylated in G2 ... Link to item Cite

A Xenopus egg factor with DNA-binding properties characteristic of terminus-specific telomeric proteins.

Journal article Genes Dev · May 1993 We have identified a Xenopus laevis protein factor that specifically recognizes vertebrate telomeric repeats at DNA ends. This factor, called Xenopus telomere end factor (XTEF), is detected predominantly in extracts of Xenopus eggs and ovaries, which are e ... Full text Link to item Cite

Casein kinase II copurifies with yeast DNA topoisomerase II and re-activates the dephosphorylated enzyme.

Journal article J Cell Sci · February 1993 Mitotic division in yeast requires the activity of topoisomerase II, a DNA topology modifying enzyme that is able to disentangle sister chromatids after DNA replication. Previous work has shown that topoisomerase II is a phosphoprotein in intact yeast cell ... Full text Link to item Cite

Regulation of topoisomerase II by phosphorylation: a role for casein kinase II.

Journal article J Cell Sci · February 1993 Full text Link to item Cite

Identification of Immunosuppressive Drug Targets in Yeast

Journal article Methods · January 1, 1993 Cells transfer information from the cell surface to the nucleus via signal transduction pathways. Although much is known about the two ends of such pathways, membrane receptors and nuclear transcription factors, the intermediate steps have remained elusive ... Full text Cite

Topoisomerase II: its functions and phosphorylation.

Journal article Antonie Van Leeuwenhoek · August 1992 The gene encoding topoisomerase II in yeast is unique and essential, required for both mitotic and meiotic proliferation. The use of temperature-sensitive mutants in topoisomerase II have demonstrated roles in the relaxation of tortional stress, reduction ... Full text Link to item Cite

Localization of RAP1 and topoisomerase II in nuclei and meiotic chromosomes of yeast.

Journal article J Cell Biol · June 1992 Topoisomerase II (topoII) and RAP1 (Repressor Activator Protein 1) are two abundant nuclear proteins with proposed structural roles in the higher-order organization of chromosomes. Both proteins co-fractionate as components of nuclear scaffolds from vegeta ... Full text Link to item Cite

Casein kinase II phosphorylates the eukaryote-specific C-terminal domain of topoisomerase II in vivo.

Journal article EMBO J · May 1992 The decatenation activity of DNA topoisomerase II is essential for viability as eukaryotic cells traverse mitosis. Phosphorylation has been shown to stimulate topoisomerase II activity in vitro. Here we show that topoisomerase II is a phosphoprotein in yea ... Full text Link to item Cite

The composition and morphology of yeast nuclear scaffolds.

Journal article J Cell Sci · July 1990 The yeast nuclear scaffold has been shown to bind with high affinity to genomic sequences that permit autonomous DNA replication of plasmids (ARS elements). We describe here conditions for the isolation of a histone-free nuclear substructure, the nuclear s ... Full text Link to item Cite

Studies on scaffold attachment sites and their relation to genome function.

Journal article Int Rev Cytol · 1989 Full text Link to item Cite

Endogenous polymers of ADP-ribose are associated with the nuclear matrix.

Journal article J Biol Chem · November 5, 1987 The metabolism of nuclear polymers of ADP-ribose has been implicated in several chromatin-associated processes. However, the distribution of endogenous ADP-ribose polymers in the nucleus or within different fractions of chromatin has not been studied. Usin ... Link to item Cite

Studies of endogenous mono(ADP-ribosylation)

Journal article Federation Proceedings · January 1, 1985 Cite

Glutamine metabolism during aerial mycelium growth of Neurospora crassa.

Journal article J Gen Microbiol · July 1984 During vegetative growth, glutamine is accumulated in the mycelium of Neurospora crassa. This high pool of glutamine seems to be required for aerial mycelium growth. Enzymes responsible for the synthesis and catabolism of glutamine were measured before and ... Full text Link to item Cite

Glutamine requirement for aerial mycelium growth in Neurospora crassa.

Journal article J Gen Microbiol · July 1984 Five amino acids are accumulated during vegetative growth of Neurospora crassa, particularly.during the prestationary growth phase. Alanine, glutamine, glutamate, arginine and ornithine.comprised over 80% of the total amino acid pool in the mycelium. Amino ... Full text Link to item Cite