Research Topics
Genomes and Genes
| Nissim HaySummaryAffiliation: University of Illinois at Chicago Country: USA Publications
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Publications
Upstream and downstream of mTORNissim Hay
Department of Biochemistry and Molecular Genetics, University of Illinois at Chicago, 60607, USA
Genes Dev 18:1926-45. 2004..We also summarize the roles of mTOR in the control of cell growth and proliferation, as well as its relevance to cancer and synaptic plasticity...
p53 strikes mTORC1 by employing sestrinsNissim Hay
Department of Biochemistry and Molecular Genetics, University of Illinois at Chicago, Chicago, IL 60607, USA
Cell Metab 8:184-5. 2008..p53 also induces a metabolic checkpoint by inhibiting the mammalian target of rapamycin complex 1 (mTORC1). Recent results by Budanov and Karin, (2008) reveal that p53 exerts its effect on mTORC1 through sestrin1 and sestrin2...
Akt isoforms and glucose homeostasis - the leptin connectionNissim Hay
Department of Biochemistry and Molecular Genetics, University of Illinois at Chicago, Chicago, IL 60607, USA
Trends Endocrinol Metab 22:66-73. 2011..The significance of these findings, together with recent observations suggesting that leptin emulates insulin action, is also discussed...- Interplay between FOXO, TOR, and AktNissim Hay
Department of Biochemistry and Molecular Genetics, University of Illinois at Chicago, IL 60607, USA
Biochim Biophys Acta 1813:1965-70. 2011..The biological significance of these regulatory circuits is discussed in this article. This article is part of a Special Issue entitled: P13K-AKT-FoxO axis in cancer and aging... - FoxOs inhibit mTORC1 and activate Akt by inducing the expression of Sestrin3 and RictorChia Chen Chen
Department of Biochemistry and Molecular Genetics, University of Illinois at Chicago, Chicago, IL 60607, USA
Dev Cell 18:592-604. 2010..Thus, under stress conditions, FoxO inhibits the anabolic activity of mTORC1, a major consumer of cellular energy, while activating Akt, which increases cellular energy metabolism, thereby maintaining cellular energy homeostasis... - Akt activates the mammalian target of rapamycin by regulating cellular ATP level and AMPK activityAnnett Hahn-Windgassen
Department of Biochemistry and Molecular Genetics, University of Illinois at Chicago, 60607, USA
J Biol Chem 280:32081-9. 2005..We propose that the activation of mTOR by Akt-mediated cellular energy and inhibition of AMPK is the predominant pathway by which Akt activates mTOR in vivo... - Akt deficiency impairs normal cell proliferation and suppresses oncogenesis in a p53-independent and mTORC1-dependent mannerJennifer E Skeen
Department of Biochemistry and Molecular Genetics, University of Illinois, Chicago, Illinois 60607, USA
Cancer Cell 10:269-80. 2006..Surprisingly, upon mTORC1 hyperactivation, the reduction in Akt activity does not impair cell proliferation and susceptibility to oncogenic transformation; thus, Akt may mediate these processes exclusively via mTORC1... - Hexokinase-mitochondria interaction mediated by Akt is required to inhibit apoptosis in the presence or absence of Bax and BakNathan Majewski
Department of Biochemistry and Molecular Genetics, University of Illinois at Chicago, Chicago, Illinois 60607, USA
Mol Cell 16:819-30. 2004.... - Role of the Akt pathway in mRNA translation of interferon-stimulated genesSurinder Kaur
Division of Hematology Oncology, Robert H Lurie Comprehensive Cancer Center, Northwestern University Medical School and Lakeside Veterans Affairs Medical Center, Chicago, IL 60611, USA
Proc Natl Acad Sci U S A 105:4808-13. 2008..Thus, activation of the Akt pathway by the IFN receptors complements the function of IFN-activated JAK-STAT pathways, by allowing mRNA translation of IFN-stimulated genes and, ultimately, the induction of the biological effects of IFNs... - mTORC1 hyperactivity inhibits serum deprivation-induced apoptosis via increased hexokinase II and GLUT1 expression, sustained Mcl-1 expression, and glycogen synthase kinase 3beta inhibitionPrashanth T Bhaskar
Department of Biochemistry and Molecular Genetics, University of Illinois at Chicago, Chicago, IL 60607, USA
Mol Cell Biol 29:5136-47. 2009..Consistently, the reduction of eIF4E levels abrogates the resistance of Tsc2(-/)(-) cells to serum deprivation-induced apoptosis... - Regulatory effects of mammalian target of rapamycin-activated pathways in type I and II interferon signalingSurinder Kaur
Robert H Lurie Comprehensive Cancer Center and Division of Hematology Oncology, Northwestern University Medical School and Lakeside Veterans Affairs Medical Center, Chicago, Illinois 60611, USA
J Biol Chem 282:1757-68. 2007..Taken altogether, our data suggest an important role for mTOR-dependent pathways in IFN signaling and identify 4E-BP1 and TSC1-TSC2 as key components in the generation of IFN-dependent biological responses... - Leptin deficiency and beta-cell dysfunction underlie type 2 diabetes in compound Akt knockout miceWilliam S Chen
University of Illinois at Chicago, Department of Biochemistry and Molecular Genetics, Chicago, IL 60607, USA
Mol Cell Biol 29:3151-62. 2009..These results uncover a new mechanism linking Akt to diabetes, provide a therapeutic strategy, and show that diabetes induced as a consequence of cancer therapy, via Akt inhibition, could be reversed by leptin therapy... - AMPK regulates NADPH homeostasis to promote tumour cell survival during energy stressSang Min Jeon
Department of Biochemistry and Molecular Genetics, College of Medicine, University of Illinois at Chicago, Chicago, Illinois 60607, USA
Nature 485:661-5. 2012.... - Activation of the p70 S6 kinase by all-trans-retinoic acid in acute promyelocytic leukemia cellsLakhvir Lal
Robert H. Lurie Comprehensive Cancer Center, Northwestern University Medical School, Chicago, IL 60611, USA
Blood 105:1669-77. 2005.... - Interferon-gamma engages the p70 S6 kinase to regulate phosphorylation of the 40S S6 ribosomal proteinFatima Lekmine
Robert H Lurie Comprehensive Cancer Center and Division of Hematology Oncology, Northwestern University Medical School and Lakeside Veterans Administration Medical Center, Chicago, IL 60611, USA
Exp Cell Res 295:173-82. 2004.... - Akt inhibits apoptosis downstream of BID cleavage via a glucose-dependent mechanism involving mitochondrial hexokinasesNathan Majewski
Department of Biochemistry and Molecular Genetics M C 669, College of Medicine, University of Illinois at Chicago, 900 S Ashland Avenue, Chicago, IL 60607, USA
Mol Cell Biol 24:730-40. 2004..These results suggest that Akt inhibits BID-mediated apoptosis downstream of BID cleavage via promotion of mitochondrial hexokinase association and antagonism of tBID-mediated BAX and BAK activation at the mitochondria... - Role of the translational repressor 4E-BP1 in the regulation of p21(Waf1/Cip1) expression by retinoidsPadma Kannan-Thulasiraman
Robert H Lurie Comprehensive Cancer Center and Division of Hematology Oncology, Northwestern University Medical School and Jesse Brown VA Medical Center, 303 East Superior, Chicago, IL, USA
Biochem Biophys Res Commun 368:983-9. 2008..Altogether, these findings strongly suggest a key regulatory role for the translational repressor 4E-BP1 in the generation of retinoid-dependent functional responses... - Akt-dependent Skp2 mRNA translation is required for exiting contact inhibition, oncogenesis, and adipogenesisVeronique Nogueira
Department of Biochemistry and Molecular Genetics, College of Medicine, University of Illinois at Chicago, Chicago, IL 60607, USA
EMBO J 31:1134-46. 2012..Skp2 re-expression in Akt-deficient preadipocytes, which are impaired in adipogenesis, is sufficient to restore adipogenesis. These results uncover the mechanism by which Akt mediates adipogenesis... - FoxM1, a critical regulator of oxidative stress during oncogenesisHyun Jung Park
Department of Biochemistry and Molecular Genetics, University of Illinois at Chicago, Chicago, IL 60607, USA
EMBO J 28:2908-18. 2009..Together, our results identify FoxM1 as a key regulator of ROS in dividing cells, and provide insights into the mechanism how tumour cells use FoxM1 to control oxidative stress to escape premature senescence and apoptosis... - Myc-ARF (alternate reading frame) interaction inhibits the functions of MycAbhishek Datta
Department of Biochemistry and Molecular Genetics, University of Illinois at Chicago, 900 S Ashland Avenue, Chicago, IL 60607, USA
J Biol Chem 279:36698-707. 2004..Our results strongly suggest that cMyc is a bona fide target of ARF and that ARF attenuates c-Myc independently of the ARF-p53 axis... - ADP-stimulated activation of Akt during integrin outside-in signaling promotes platelet spreading by inhibiting glycogen synthase kinase-3βKelly A O'Brien
Department of Pharmacology, University of Illinois College of Medicine, 835 S Wolcott Avenue, Chicago, IL 60612, USA
Arterioscler Thromb Vasc Biol 32:2232-40. 2012..We sought to determine the role of the Akt family of serine/threonine kinases and activation mechanisms of the PI3K/Akt pathway in outside-in signaling... - Akt activation emulates Chk1 inhibition and Bcl2 overexpression and abrogates G2 cell cycle checkpoint by inhibiting BRCA1 fociIvana Tonic
Department of Biochemistry and Molecular Genetics, University of Illinois at Chicago, Chicago, IL 60607, USA
J Biol Chem 285:23790-8. 2010..We show that Akt inhibits BRCA1 function that induces G2 cell cycle arrest. Akt prevents the translocation of BRCA1 to DNA damage foci and, thereby, inhibiting the activation of Chk1 following DNA damage... - The deficiency of Akt1 is sufficient to suppress tumor development in Pten+/- miceMei Ling Chen
Department of Biochemistry and Molecular Genetics, University of Illinois at Chicago, Chicago, Illinois 60607, USA
Genes Dev 20:1569-74. 2006..Even haplodeficiency of Akt1 was sufficient to markedly attenuate the development of high-grade prostate intraepithelial neoplasia (PIN) and endometrial carcinoma. These results have significant implications for cancer therapy... - Regulatory effects of mammalian target of rapamycin-mediated signals in the generation of arsenic trioxide responsesJessica K Altman
Robert H Lurie Comprehensive Cancer Center and Division of Hematology Oncology, Northwestern University Medical School, Lakeside Veterans Affairs Medical Center, Chicago, Illinois 60611, USA
J Biol Chem 283:1992-2001. 2008.... - Akt determines replicative senescence and oxidative or oncogenic premature senescence and sensitizes cells to oxidative apoptosisVeronique Nogueira
Department of Biochemistry and Molecular Genetics, University of Illinois at Chicago, Chicago, IL 60607, USA
Cancer Cell 14:458-70. 2008..Given that rapamycin alone is mainly cytostatic, this constitutes a strategy for cancer therapy that selectively eradicates cancer cells via Akt activation... - The two TORCs and AktPrashanth T Bhaskar
Department of Biochemistry and Molecular Genetics, University of Illinois at Chicago College of Medicine, 900 South Ashland Avenue, Chicago, IL 60607, USA
Dev Cell 12:487-502. 2007..This review highlights recent developments aimed at deciphering the interplay between Akt and mTORCs as well as their role in embryonic development and in cancer... - An important role for Akt3 in platelet activation and thrombosisKelly A O'Brien
Department of Pharmacology, University of Illinois at Chicago, Chicago, IL, USA
Blood 118:4215-23. 2011..Importantly, Akt3(-/-) mice showed retardation in FeCl₃-induced carotid artery thrombosis in vivo. Thus, Akt3 plays an important and distinct role in platelet activation and in thrombosis... - Activation of the p70 S6 kinase and phosphorylation of the 4E-BP1 repressor of mRNA translation by type I interferonsFatima Lekmine
Robert H Lurie Comprehensive Cancer Center and Division of Hematology Oncology, Northwestern University Medical School and Lakeside Veterans Administration Medical Center, Chicago, Illinois 60611, USA
J Biol Chem 278:27772-80. 2003..Altogether, our data establish that the Type I IFN receptor-activated PI 3'-kinase pathway mediates activation of the p70 S6 kinase and inactivation of 4E-BP1, to regulate mRNA translation and induction of Type I IFN responses... - Immunohistochemical expression of components of the Akt-mTORC1 pathway is associated with hepatocellular carcinoma in patients with chronic liver diseaseScott J Cotler
Department of Medicine, The University of Illinois at Chicago, Chicago, IL 60612, USA
Dig Dis Sci 53:844-9. 2008..Activation of the Akt-mTORC1 signaling pathway was evaluated in premalignant and hepatocellular carcinoma (HCC) lesions by assessing the expression of pS6, an Akt effector, and PTEN, an Akt suppressor... - Statin-dependent suppression of the Akt/mammalian target of rapamycin signaling cascade and programmed cell death 4 up-regulation in renal cell carcinomaJennifer Woodard
Robert H Lurie Comprehensive Cancer Center, Northwestern University Medical School, Chicago, Illinois, USA
Clin Cancer Res 14:4640-9. 2008.... - Deregulation of FoxM1b leads to tumour metastasisHyun Jung Park
Department of Biochemistry and Molecular Genetics, UIC Cancer Center, College of Medicine, University of Illinois at Chicago, Chicago, IL, USA
EMBO Mol Med 3:21-34. 2011..The observations indicate that FoxM1b is a potent activator of tumour metastasis and that the Arf-mediated inhibition of FoxM1b is a critical mechanism for suppression of tumour metastasis... - Mitochondrial hexokinases: guardians of the mitochondriaR Brooks Robey
Department of Medicine, University of Illinois at Chicago, 60607 7170, USA
Cell Cycle 4:654-8. 2005..We also propose that this "guardian" function of mtHK may be specifically exploited for therapeutic purposes... - c-Myc sensitization to oxygen deprivation-induced cell death is dependent on Bax/Bak, but is independent of p53 and hypoxia-inducible factor-1Joslyn K Brunelle
Department of Medicine, Northwestern University Medical School, Chicago, Illinois 60611 3010, USA
J Biol Chem 279:4305-12. 2004..Thus, oxygen deprivation-induced cell death in fibroblasts with deregulated expression of c-Myc is independent of p53 or HIF-1 status, but is dependent on the Bcl-2 family member Bax or Bak to initiate mitochondrial dependent cell death... - Akt isoforms differentially regulate neutrophil functionsJia Chen
Department of Pharmacology, University of Illinois College of Medicine, Chicago, IL 60612, USA
Blood 115:4237-46. 2010..These results demonstrate a predominant role of Akt2 in regulating neutrophil functions and provide evidence for differential activation of the 2 Akt isoforms in neutrophils... - The Akt-mTOR tango and its relevance to cancerNissim Hay
Department of Biochemistry and Molecular Genetics, University of Illinois at Chicago College of Medicine, 60607, USA
Cancer Cell 8:179-83. 2005..Two recent studies used mouse genetics to assess the roles of PTEN and TSC2 in cancer, underscoring the importance of Akt-mTOR interplay for cancer progression and therapy... - AMPK as a therapeutic target in renal cell carcinomaJennifer Woodard
Robert H Lurie Comprehensive Cancer Center and Division of Hematology Oncology, Northwestern University Medical School and Jesse Brown VA Medical Center, Chicago, IL, USA
Cancer Biol Ther 10:1168-77. 2010..Altogether, our studies demonstrate that AMPK plays critical regulatory roles in the regulation of growth of RCC cells and raise the prospect of future use of AMPK activators in the treatment of renal cell carcinoma in humans... - The Akt1 isoform is required for optimal IFN-β transcription through direct phosphorylation of β-cateninBenjamin N Gantner
Department of Pharmacology, College of Medicine, University of Illinois at Chicago, Chicago, IL 60612, USA
J Immunol 189:3104-11. 2012..Taken together, these results demonstrate that the Akt1 isoform is required for β-catenin-mediated promotion of IFN-β transcription downstream of TLR3 activation... - The matrix protein CCN1 (CYR61) induces apoptosis in fibroblastsViktor Todorovic
Department of Biochemistry and Molecular Genetics, University of Illinois at Chicago College of Medicine, Chicago, IL 60607, USA
J Cell Biol 171:559-68. 2005.... - Akt-phosphorylated mitogen-activated kinase-activating death domain protein (MADD) inhibits TRAIL-induced apoptosis by blocking Fas-associated death domain (FADD) association with death receptor 4Peifeng Li
Department of Microbiology and Immunology, University of Illinois at Chicago, Chicago, Illinois 60612, USA
J Biol Chem 285:22713-22. 2010..Because Akt is active in most cancer cells and phosphorylated MADD confers resistance to TRAIL-induced apoptosis, co-targeting Akt-MADD axis is likely to increase efficacy of TRAIL-based therapies... - A phosphoinositide 3-kinase-AKT-nitric oxide-cGMP signaling pathway in stimulating platelet secretion and aggregationAleksandra Stojanovic
Department of Pharmacology, University of Illinois College of Medicine, 835 South Wolcott Avenue, Chicago, IL 60612, USA
J Biol Chem 281:16333-9. 2006..Thus, this study delineates a novel platelet activation pathway involving sequential activation of PI3K, Akt, nitric-oxide synthase 3, sGC, and cGMP-dependent protein kinase... - Dwarfism, impaired skin development, skeletal muscle atrophy, delayed bone development, and impeded adipogenesis in mice lacking Akt1 and Akt2Xiao ding Peng
Department of Molecular Genetics, College of Medicine, University of Illinois at Chicago, Chicago, Illinois 60607, USA
Genes Dev 17:1352-65. 2003.... - Activation of Akt/protein kinase B overcomes a G(2)/m cell cycle checkpoint induced by DNA damageEugene S Kandel
Department of Molecular Genetics, College of Medicine, University of Illinois at Chicago, Chicago, Illinois 60607, USA
Mol Cell Biol 22:7831-41. 2002..We suggest that this new activity of Akt in conjunction with its antiapoptotic activity may contribute to genetic instability and could explain its frequent activation in human cancers... - Bcl-2 family members and functional electron transport chain regulate oxygen deprivation-induced cell deathDavid S McClintock
Division of Pulmonary and Critical Care Medicine, Department of Medicine, Northwestern University Medical School, Chicago, Illinois 60601-3010, USA
Mol Cell Biol 22:94-104. 2002..Proapoptotic Bcl-2 family members and a functional electron transport chain are required to initiate cell death in response to oxygen deprivation... - Inhibition of Chk1 by activated PKB/AktFrank W King
Cancer Research Institute, University of California San Francisco, 94115, USA
Cell Cycle 3:634-7. 2004..Inhibition of these steps provides a plausible explanation for the observed attenuation of Chk1 activation by activated PKB after DNA damage... - A hypoxia-independent hypoxia-inducible factor-1 activation pathway induced by phosphatidylinositol-3 kinase/Akt in HER2 overexpressing cellsYan M Li
Department of Molecular and Cellular Oncology, University of Texas M.D. Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX 77030, USA
Cancer Res 65:3257-63. 2005.... - Increased hexokinase activity, of either ectopic or endogenous origin, protects renal epithelial cells against acute oxidant-induced cell deathJane M Bryson
Department of Medicine, College of Medicine, University of Illinois, Chicago 60612, USA
J Biol Chem 277:11392-400. 2002..These findings also support the contention that HKs contribute to the protective effects of growth factors... - Gadd45 beta mediates the protective effects of CD40 costimulation against Fas-induced apoptosisFrancesca Zazzeroni
Gwen Knapp Center for Lupus and Immunoolgy Research, Ben May Institute, and Committee on Immunology, University of Chicago, IL 60637, USA
Blood 102:3270-9. 2003..These findings identify Gadd45 beta as a critical mediator of the prosurvival response to CD40 stimulation and provide important new insights into the apoptotic mechanism that is triggered by Fas in B cells... - Impaired platelet responses to thrombin and collagen in AKT-1-deficient miceJuhua Chen
Joseph J Jacobs Center for Thrombosis and Vascular Biology, Department of Molecular Cardiology, Joseph J Jacobs Center for Thrombosis and Vascular Biology, Cleveland Clinic Foundation, NB50, 9500 Euclid Ave, Cleveland, OH 44195, USA
Blood 104:1703-10. 2004..As a consequence of impaired alpha(IIb)beta(3) activation and platelet aggregation, Akt-1 null mice showed significantly longer bleeding times than wild-type mice... - The role of Akt in the signaling pathway of the glycoprotein Ib-IX induced platelet activationHong Yin
Department of Pharmacology, University of Illinois at Chicago 60612, USA
Blood 111:658-65. 2008..Thus, Akt1 and Akt2 mediate GPIb-IX signaling via the cGMP-dependent signaling pathway... - Akt1 governs breast cancer progression in vivoXiaoming Ju
Department of Cancer Biology, Kimmel Cancer Center, Thomas Jefferson University, 233 South 10th Street, Philadelphia, PA 19107, USA
Proc Natl Acad Sci U S A 104:7438-43. 2007..Akt1 governs MEC polarity, migratory directionality and breast cancer onset induced by ErbB2 in vivo...
Research Grants
- Akt, cellular senescence, and lifespanNissim Hay; Fiscal Year: 2007....
- P13K/PTEN/Akt signaling and the genesis of cancerNissim Hay; Fiscal Year: 2007..The second part of this grant application will address these issues at the organism level and assess the susceptibility of various Akt knockout (KO) mice to the development of various neoplasia. ..
- The role of Akt in cell survival and cell growthNissim Hay; Fiscal Year: 2007..We will use the Akt KO mice and cells derived from these mice to provide genetic evidence for the role of Akt in these processes. ..
- The role of Akt in cell survival and cell growthNissim Hay; Fiscal Year: 2010..Studies are also intended to delineate the role of this pathway in the development of hepatocellular carcinoma. ..
- Akt, cellular senescence, and lifespanNissim Hay; Fiscal Year: 2010..abstract_text> ..
- P13K/PTEN/Akt (PKB), Signaling and genesis of cancerNissim Hay; Fiscal Year: 2005....
- MECHANISM OF SERINE/THREONINE KINASE SURVIVAL PROMOTIONNissim Hay; Fiscal Year: 2002..cascade at the level of Bcl-2 family members, integrity of mitochondria, caspase activity or Ced-4/Apaf-1? (3) Does Akt promote survival by increasing cell-cell adhesion and/or intracellular levels of b-catenin via inhibition of GSK3? ..
- P13K/PTEN/Akt signaling and the genesis of cancerNissim Hay; Fiscal Year: 2010..The second part of this grant application will address these issues at the organism level and assess the susceptibility of various Akt knockout (KO) mice to the development of various neoplasia. ..