Research Topics
Genomes and Genes | Ganes SenSummaryAffiliation: Cleveland Clinic Foundation Country: USA Publications
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Viruses and interferonsG C Sen
Department of Molecular Biology, Lerner Research Institute, The Cleveland Clinic Foundation, 9500 Euclid Avenue, Cleveland, Ohio 44195, USA
Annu Rev Microbiol 55:255-81. 2001..Thus, in nature interferons and viruses maintain an equilibrium that allows regulated viral replication...- Transcriptional signaling by double-stranded RNA: role of TLR3Ganes C Sen
Department of Molecular Genetics NC20, The Lerner Research Institute, The Cleveland Clinic Foundation, 9500 Euclid Avenue, Cleveland, OH 44195, USA
Cytokine Growth Factor Rev 16:1-14. 2005..Specifically, we discuss the roles of receptor tyrosine phosphorylation, PI3 kinase and two-step activation of the transcription factors, IRF-3 and NF-kappaB, in mediating TLR3-signaling... - Novel characteristics of the function and induction of murine p56 family proteinsVolker Fensterl
Department of Molecular Genetics NE20, Cleveland Clinic, 9500 Euclid Avenue, Cleveland, OH 44195, USA
J Virol 82:11045-53. 2008..These results revealed novel cell type-, inducer-, and gene-specific regulation of the ISG56 family of genes... - The interferon-stimulated genes: targets of direct signaling by interferons, double-stranded RNA, and virusesG C Sen
Department of Molecular Genetics NE20, The Lerner Research Institute, Cleveland Clinic, 9500 Euclid Avenue, Cleveland, OH 44195, USA
Curr Top Microbiol Immunol 316:233-50. 2007..We also review the biochemical and cellular properties of the protein products of a selected number of these genes including ISG56, ISG54, and ISG15... - The IRF-3/Bax-mediated apoptotic pathway, activated by viral cytoplasmic RNA and DNA, inhibits virus replicationSaurabh Chattopadhyay
Cleveland Clinic, Department of Molecular Genetics, 9500 Euclid Avenue, NE20, Cleveland, OH 44195, USA
J Virol 85:3708-16. 2011..Our results clearly demonstrate that the IRF-3/Bax-mediated apoptotic signaling branch contributes significantly to the host's protection from viral infection and consequent pathogenesis... - Tissue-specific and inducer-specific differential induction of ISG56 and ISG54 in miceFulvia Terenzi
Department of Molecular Genetics NE20, The Lewrnert research Institute, Cleveland Clinic, 9500 Euclid Avenue, Cleveland, OH 44195, USA
J Virol 81:8656-65. 2007..Furthermore, our findings provide the first evidence of a differential pattern of expression of ISG54 and ISG56 genes by IFN-alpha and IFN-beta... - Analysis of genes induced by Sendai virus infection of mutant cell lines reveals essential roles of interferon regulatory factor 3, NF-kappaB, and interferon but not toll-like receptor 3Christopher P Elco
Department of Molecular Biology, Lerner Research Institute, The Cleveland Clinic Foundation, 9500 Euclid Ave, Cleveland, OH 44195, USA
J Virol 79:3920-9. 2005..Thus, IRF-3 can suppress the expression of NF-kappaB-dependent genes in SeV-infected cells... - Maintenance of normal blood pressure and renal functions are independent effects of angiotensin-converting enzymeSean P Kessler
Department of Molecular Biology, Lerner Research Institute, Cleveland Clinic Foundation, Cleveland, Ohio 44195, USA
J Biol Chem 278:21105-12. 2003..These results also demonstrate that ACE-mediated blood pressure maintenance can be dissociated from its role in maintaining renal structure and functions... - Vascular expression of germinal ACE fails to maintain normal blood pressure in ACE-/- miceSean P Kessler
Department of Molecular Genetics, Lerner Research Institute, 9500 Euclid Ave, Cleveland, Ohio 44195, USA
FASEB J 21:156-66. 2007..This study demonstrated that gACE, even when expressed in the vasculature, could not functionally substitute for sACE... - Endoplasmic reticulum stress induces hyaluronan deposition and leukocyte adhesionAlana K Majors
Department of Immunology, NB30, Cleveland Clinic Foundation, 9500 Euclid Avenue, Cleveland, OH 44195, USA
J Biol Chem 278:47223-31. 2003..These results indicate that ER stress may contribute to chronic inflammation by forming a hyaluronan-rich extracellular matrix that is conducive to leukocyte binding... - Novel functions of proteins encoded by viral stress-inducible genesSaumendra N Sarkar
Department of Molecular Biology/NC20, The Lerner Research Institute, The Cleveland Clinic Foundation, 9500 Euclid Avenue, Cleveland, OH 44195, USA
Pharmacol Ther 103:245-59. 2004..Finally, we will present a future perspective and point out the main gaps of our knowledge in the field... - Interferons at age 50: past, current and future impact on biomedicineErnest C Borden
Taussig Cancer Center, Case Comprehensive Cancer Center, Mellen Center for Multiple Sclerosis, and Lerner Research Institute, The Cleveland Clinic, 9500 Euclid Avenue, Cleveland, Ohio 44195, USA
Nat Rev Drug Discov 6:975-90. 2007..Our goal is to offer a molecular and clinical perspective that will enable IFNs or their TLR agonist inducers to reach their full clinical potential... - Distinct induction patterns and functions of two closely related interferon-inducible human genes, ISG54 and ISG56Fulvia Terenzi
Department of Molecular Genetics, Lerner Research Institute, Cleveland Clinic, Cleveland, Ohio 44195, USA
J Biol Chem 281:34064-71. 2006..Thus, although similar in structure, the human P54 and P56 proteins are induced differently and function differently... - Nephron function in transgenic mice with selective vascular or tubular expression of Angiotensin-converting enzymeSean P Kessler
Department of Molecular Genetics, Lerner Research Institute, Cleveland, OH 44195, USA
J Am Soc Nephrol 16:3535-42. 2005..Our results demonstrate that vascular expression of sACE can largely but not completely restore TGF regulation of GFR. Proximal fluid reabsorption in the chronic absence of proximal tubule ACE is normal... - Immunology. A viral on/off switch for interferonBryan R G Williams
Department of Cancer Biology, Lerner Research Institute, Cleveland Clinic Foundation, OH 44195, USA
Science 300:1100-1. 2003 - Novel roles of TLR3 tyrosine phosphorylation and PI3 kinase in double-stranded RNA signalingSaumendra N Sarkar
Department of Molecular Biology, The Lerner Research Institute, Cleveland Clinic Foundation, Cleveland, Ohio 44195, USA
Nat Struct Mol Biol 11:1060-7. 2004..Thus, the PI3K-Akt pathway plays an essential role in TLR3-mediated gene induction... - Select paramyxoviral V proteins inhibit IRF3 activation by acting as alternative substrates for inhibitor of kappaB kinase epsilon (IKKe)/TBK1Lenette L Lu
Department of Molecular Genetics, Lerner Research Institute, Cleveland Clinic, Cleveland, OH 44195, USA
J Biol Chem 283:14269-76. 2008.... - Double-stranded RNA signaling by Toll-like receptor 3 requires specific tyrosine residues in its cytoplasmic domainSaumendra N Sarkar
Department of Molecular Biology, The Lerner Research Institute, Cleveland Clinic Foundation, Cleveland, Ohio 44195, USA
J Biol Chem 278:4393-6. 2003..Our results provide the first demonstration of the importance of TLR3 cytoplasmic tyrosine residues in dsRNA signaling... - Induction and mode of action of the viral stress-inducible murine proteins, P56 and P54Fulvia Terenzi
Department of Molecular Genetics/NE20, The Lerner Research Institute, Cleveland Clinic Foundation, Cleveland, OH 44195, USA
Virology 340:116-24. 2005..Thus, members of the human and murine P56 family have similar but non-identical functions... - Crystal structure of the 2'-specific and double-stranded RNA-activated interferon-induced antiviral protein 2'-5'-oligoadenylate synthetaseRune Hartmann
Department of Molecular Cardiology and Center for Structural Biology, Cleveland Clinic Foundation, Cleveland, OH 44195, USA
Mol Cell 12:1173-85. 2003.... - The germinal isozyme of angiotensin-converting enzyme can substitute for the somatic isozyme in maintaining normal renal structure and functionsSean P Kessler
Department of Molecular Biology, Lerner Research Institute, Cleveland Clinic Foundation, Cleveland, Ohio 44195, USA
J Biol Chem 277:4271-6. 2002..This result demonstrated that circulating germinal ACE is sufficient for maintaining normal kidney structure and fluid homeostasis but insufficient for restoring blood pressure to normal levels... - IRF-3-dependent, NFkappa B- and JNK-independent activation of the 561 and IFN-beta genes in response to double-stranded RNAKristi L Peters
Department of Molecular Biology, The Lerner Research Institute, The Cleveland Clinic Foundation, 9500 Euclid Avenue, Cleveland, OH 44195, USA
Proc Natl Acad Sci U S A 99:6322-7. 2002..Therefore, IRF-3 activation by dsRNA is sufficient to induce the transcription of genes with simple promoters such as 561 as well as complex promoters such as IFN-beta... - PACT-mediated enhancement of reporter gene expression at the translational levelShoudong Li
Department of Molecular Biology, The Lerner Research Institute, Cleveland Clinic Foundation, Cleveland, OH 44195, USA
J Interferon Cytokine Res 23:689-97. 2003..Thus, different domains of PACT can either promote or inhibit translation by appropriately modulating the status of eIF2alpha phosphorylation... - Binding of the influenza A virus NS1 protein to PKR mediates the inhibition of its activation by either PACT or double-stranded RNAShoudong Li
Department of Molecular Genetics, Lerner Research Institute, Cleveland Clinic Foundation, Cleveland, OH 44195, USA
Virology 349:13-21. 2006..In addition, we demonstrated that PKR activation is inhibited in cells infected with a recombinant influenza A virus expressing NS1A mutant protein that cannot bind RNA, as is the case in cells infected with wild-type influenza A virus... - Mouse p56 blocks a distinct function of eukaryotic initiation factor 3 in translation initiationDaniel J Hui
Department of Molecular Biology, The Lerner Research Institute, Cleveland Clinic Foundation, Cleveland, Ohio 44195, USA
J Biol Chem 280:3433-40. 2005..eIF3.ternary complex. Thus, mouse and human p56 proteins block different functions of eIF3 by binding to its different subunits... - Interferon-inducible protein, P56, inhibits HPV DNA replication by binding to the viral protein E1Fulvia Terenzi
Department of Molecular Genetics, The Lerner Research Institute, Cleveland Clinic, Cleveland, OH 44195, USA
EMBO J 27:3311-21. 2008..In vitro, recombinant P56, or a small fragment derived from it, inhibited the DNA helicase activity of E1 and E1-mediated HPV DNA replication. These observations delineate the molecular mechanism of IFN's antiviral action against HPV... - The p59 oligoadenylate synthetase-like protein possesses antiviral activity that requires the C-terminal ubiquitin-like domainJoao Marques
Department of Cancer Biology, The Cleveland Foundation, 9500 Euclid Avenue, Cleveland, OH 44195, USA
J Gen Virol 89:2767-72. 2008..Taken together our results indicate that p59 is indeed an antiviral protein that works through a novel mechanism distinct from other OAS proteins... - Biochemical analysis of PKR activation by PACTGregory A Peters
Department of Molecular Genetics, Lerner Research Institute, The Cleveland Clinic Foundation, Cleveland, Ohio 44195, USA
Biochemistry 48:7441-7. 2009..These results indicate that stress-induced phosphorylation of specific serine residues in domain 3 of PACT increases its affinity for PKR, which leads to better activation of PKR and resultant eIF-2alpha phosphorylation... - Viral stress-inducible genesGanes C Sen
Department of Molecular Genetics, The Lerner Research Institute, Cleveland Clinic Foundation, Cleveland, Ohio 44195, USA
Adv Virus Res 70:233-63. 2007..Thus, in an infected cell, equilibrium is reached between the virus and the cell with regards to the viral stress-inducible genes... - Two tyrosine residues of Toll-like receptor 3 trigger different steps of NF-kappa B activationSaumendra N Sarkar
Department of Molecular Genetics, Lerner Research Institute, Cleveland Clinic, Cleveland, Ohio 44195, USA
J Biol Chem 282:3423-7. 2007..Thus, two phosphotyrosine residues of TLR3 activate two distinct pathways, one leading to NF-kappaB release and the other leading to its phosphorylation... - Natural mutations in a 2'-5' oligoadenylate synthetase transgene revealed residues essential for enzyme activitySaumendra N Sarkar
Department of Molecular Biology, The Lerner Research Institute, Cleveland Clinic Foundation, Cleveland, Ohio 44195, USA
Biochemistry 44:6837-43. 2005..This study illustrates the power of using natural mutations in transgenes as guides for studying structure-function relationships of proteins... - Phosphorylation of specific serine residues in the PKR activation domain of PACT is essential for its ability to mediate apoptosisGregory A Peters
Department of Molecular Genetics, Lerner Research Institute, Cleveland Clinic Foundation, Cleveland, Ohio 44195, USA
J Biol Chem 281:35129-36. 2006..These results indicate that phosphorylation of specific serine residues in the activation domain of PACT is the major mode of transmission of cellular stress response to PKR... - Viral stress-inducible protein p56 inhibits translation by blocking the interaction of eIF3 with the ternary complex eIF2.GTP.Met-tRNAiDaniel J Hui
Department of Molecular Biology, The Lerner Research Institute, Cleveland Clinic Foundation, and Graduate Program in Molecular Virology, Case Western Reserve University School of Medicine, Ohio, USA
J Biol Chem 278:39477-82. 2003..Whereas cap-dependent initiation was severely inhibited by p56, internal ribosomal entry site-mediated translation appeared to be insensitive to p56... - Assays for the interferon-induced enzyme 2',5' oligoadenylate synthetasesSaumendra N Sarkar
Department of Molecular Biology, The Lerner Research Institute, Cleaveland Clinic Foundation, OH, USA
Methods Mol Med 116:81-101. 2005..Recently, it has also been implicated in prostate cancer metastasis. In this chapter we describe several methodologies for studying biochemical and physiological properties of the 2-5 (A) synthetase-RNase L pathway... - The proapoptotic 9-2 isozyme of 2-5 (A) synthetase cannot substitute for the sperm functions of the proapoptotic protein, BaxJanette B Gomos
The Lerner Research Institute, Department of Molecular Biology, The Cleveland Clinic Foundation, Cleveland, OH 44195, USA
J Interferon Cytokine Res 22:199-206. 2002..The male experimental mice were sterile, and their testes maintained the structural abnormality found in Bax(-/-) mice. Thus, the male reproduction functions of Bax could not be replaced by the 9-2 isozyme of 2-5 (A) synthetase... - Calmodulin binds to the cytoplasmic domain of angiotensin-converting enzyme and regulates its phosphorylation and cleavage secretionSaurabh Chattopadhyay
Department of Molecular Cardiology, Lerner Research Institute, The Cleveland Clinic Foundation, Cleveland, Ohio 44195, USA
J Biol Chem 280:33847-55. 2005..These results demonstrate that, although CaMI and PMA can enhance both cleavage secretion of ACE and its dephosphorylation, the two effects are not mutually interdependent... - Phosphatidylinositol 3-kinase signaling delays sendai virus-induced apoptosis by preventing XIAP degradationChristine L White
Department of Molecular Genetics NE20, Cleveland Clinic, 9500 Euclid Avenue, Cleveland, OH 44195, USA
J Virol 85:5224-7. 2011..Thus, SeV infection-mediated apoptosis is temporally regulated by the prevention of XIAP degradation by PI3K... - Interferons and viral infectionsVolker Fensterl
Department of Molecular Genetics, The Lerner Research Institute, Cleveland Clinic, Cleveland, Ohio 44195, USA
Biofactors 35:14-20. 2009..The unique biological functions of interferons have led to their therapeutic use in the treatment of diseases such as hepatitis, multiple sclerosis, and certain leukemias... - IRF-3 activation by Sendai virus infection is required for cellular apoptosis and avoidance of persistenceKristi Peters
Department of Molecular Genetics, Lerner Research Institute, Cleveland Clinic, Cleveland, Ohio 44195, USA
J Virol 82:3500-8. 2008..These results demonstrated that in our model system, IRF-3 controlled the fate of the SeV-infected cells by promoting apoptosis and preventing persistence... - The double-stranded RNA-binding protein, PACT, is required for postnatal anterior pituitary proliferationGregory A Peters
Department of Molecular Genetics, The Lerner Research Institute, Cleveland Clinic Foundation, Cleveland, OH 44195, USA
Proc Natl Acad Sci U S A 106:10696-701. 2009..Our study revealed a physiologically significant role for PACT in cell proliferation and an essential role of a dsRNA-binding protein in mammalian pituitary expansion... - Viral apoptosis is induced by IRF-3-mediated activation of BaxSaurabh Chattopadhyay
Department of Molecular Genetics, Lerner Research Institute, Cleveland Clinic, Cleveland, OH 44195, USA
EMBO J 29:1762-73. 2010..Thus, IRF-3 is a dual-action cytoplasmic protein that, upon activation, translocates to the nucleus or to the mitochondrion and triggers two complementary antiviral responses of the infected cell... - The interferon (IFN)-induced GTPase, mGBP-2. Role in IFN-gamma-induced murine fibroblast proliferationVictoria Y Gorbacheva
Department of Molecular Biology, Lerner Research Institute, The Cleveland Clinic Foundation, Cleveland, Ohio 44195, USA
J Biol Chem 277:6080-7. 2002.... - Crisscross enzymatic reaction between the two molecules in the active dimeric P69 form of the 2'-5' oligodenylate synthetaseSaumendra N Sarkar
Department of Molecular Biology, The Lerner Research Institute, Cleveland Clinic Foundation, Cleveland, Ohio 44195, USA
J Biol Chem 277:44760-4. 2002..These results allowed us to design a mutant protein that acted as a dominant-negative inhibitor of wt P69 but not of another isozyme of 2-5 (A) synthetase... - A small region in the angiotensin-converting enzyme distal ectodomain is required for cleavage-secretion of the protein at the plasma membraneSaurabh Chattopadhyay
Department of Molecular Genetics, Lerner Research Institute, Cleveland Clinic, Cleveland, Ohio 44195, USA
Biochemistry 47:8335-41. 2008..This conclusion was further supported by our observation that secreted ACE inhibited cell-bound ACE cleavage-secretion, although the secreted form did not contain the cleavage site... - Stat1 required for interferon-inducible but not constitutive responsiveness to extracellular dsRNAChristopher P Elco
Graduate Program in Molecular Virology, Case Western Reserve University School of Medicine, Cleveland, OH 44106, USA
J Interferon Cytokine Res 27:411-24. 2007..Our results demonstrate that Stat1 is critical for IFN-induced, not basal, responsiveness to extracellular dsRNA... - Molecular basis for PKR activation by PACT or dsRNAShoudong Li
Department of Molecular Genetics NE20, Lerner Research Institute, Cleveland Clinic Foundation, 9500 Euclid Avenue, Cleveland, OH 44195, USA
Proc Natl Acad Sci U S A 103:10005-10. 2006..Furthermore, a short decoy peptide, representing PBM, was able to activate PKR by interfering with the intramolecular interaction. These observations suggest a model for PKR activation upon binding of dsRNA or PACT... - Alpha interferon induces distinct translational control programs to suppress hepatitis C virus RNA replicationChunfu Wang
Department of Microbiology, University of Texas Southwestern Medical Center, Dallas, Texas 75390-9048, USA
J Virol 77:3898-912. 2003..We conclude that IFN blocks HCV replication through translational control programs involving PKR and P56 to, respectively, target eIF2- and eIF3-dependent steps in the viral RNA translation initiation process... - Transcriptional profiling of interferon regulatory factor 3 target genes: direct involvement in the regulation of interferon-stimulated genesNathalie Grandvaux
Terry Fox Molecular Oncology Group, Lady Davis Institute for Medical Research, McGill University, Montreal, Quebec H3T 1E2, Canada
J Virol 76:5532-9. 2002.... - Long-term effect of interferon on keratinocytes that maintain human papillomavirus type 31Yijan E Chang
Department of Microbiology-Immunology, The Fineberg Medical School, Northwestern University, Chicago, Illinois 60611, USA
J Virol 76:8864-74. 2002..These studies indicate that cells maintaining HPV episomes are highly sensitive to interferon treatment but that resistant populations arise quickly... - Hitching RIG to actionGanes C Sen
Nat Immunol 6:1074-6. 2005 - Replication of hepatitis C virus (HCV) RNA in mouse embryonic fibroblasts: protein kinase R (PKR)-dependent and PKR-independent mechanisms for controlling HCV RNA replication and mediating interferon activitiesKyung-Soo Chang
Department of Microbiology, Immunology, and Molecular Genetics, University of Kentucky College of Medicine, 800 Rose Street, Lexington, KY 40536-0298, USA
J Virol 80:7364-74. 2006.... - A site on the influenza A virus NS1 protein mediates both inhibition of PKR activation and temporal regulation of viral RNA synthesisJi Young Min
Institute for Cellular and Molecular Biology, Section of Molecular Genetics and Microbiology, room 2 122, 2500 Speedway, University of Texas at Austin, Austin, TX 78712, USA
Virology 363:236-43. 2007..This interaction would occur in the nucleus, whereas PKR would bind to NS1A proteins in the cytoplasm prior to their import into the nucleus... - The role of PACT in mediating gene induction, PKR activation, and apoptosis in response to diverse stimuliJoao T Marques
Department of Molecular Genetics, Cleveland Clinic, Cleveland, Ohio 44195, USA
J Interferon Cytokine Res 28:469-76. 2008..Taken together, our results reinforce the importance of genetic loss of function analysis to infer protein function... - Coordinated regulation and widespread cellular expression of interferon-stimulated genes (ISG) ISG-49, ISG-54, and ISG-56 in the central nervous system after infection with distinct virusesChristie Wacher
School of Molecular and Microbial Biosciences, University of Sydney, Sydney, NSW 2006, Australia
J Virol 81:860-71. 2007..These findings suggest a dominant role for the ISG-49, ISG-54, and ISG-56 genes in the host response to different viruses in the central nervous system, where, particularly in neurons, these genes may have nonredundant functions...
Research Grants
- Viral Stress-inducible Gene ExpressionGanes Sen; Fiscal Year: 2005..These studies will illuminate the modes of cross-talk between the TLR and the Jak-STAT signaling pathways for appropriate gene induction in virus-infected cells. ..
- ANGIOTENSIN CONVERTING ENZYME GENE EXPRESSIONGanes Sen; Fiscal Year: 2005..abstract_text> ..
- ANTIVIRAL ACTIONS OF INTERFERONSGanes Sen; Fiscal Year: 2007..abstract_text> ..
- Antiotensin converting enzyme gene expressionGanes Sen; Fiscal Year: 2009....
- Cellular Determinants of Apoptosis in Virus-Infected CellsGanes Sen; Fiscal Year: 2009..For this purpose, the different steps of the viral life cycle will be examined. Moreover, the status of the innate immune response in the persistently infected cells will be evaluated. ..
- Antiotensin converting enzyme gene expressionGanes C Sen; Fiscal Year: 2010....
- ANTIVIRAL ACTIONS OF INTERFERONSGanes C Sen; Fiscal Year: 2010..For combating virus infection, the interferon system is the most important component of the mammalian innate immune system and here we propose to study its functions. ..
- ANTIVIRAL ACTIONS OF INTERFERONSGanes Sen; Fiscal Year: 2003..For these studies, advantage will be taken of an in vitro differentiation system of keratinocytes that allows HPV gene expression, replication and morphogenesis. ..
- ANGIOTENSIN CONVERTING ENZYME GENE EXPRESSIONGanes Sen; Fiscal Year: 1993..Finally, we will determine the enzymatic properties of cell-bound ACE by expressing a non-secretable form of ACE. The information obtained from the last aim ,will be valuable for understanding localized action of ACE in the body...
- ANGIOTENSIN CONVERTING ENZYME GENE EXPRESSIONGanes Sen; Fiscal Year: 2001..These studies may also lead to the identification of additional physiological substrates of this important enzyme. ..
- Cellular Determinants of Apoptosis in Virus-Infected CellsGanes C Sen; Fiscal Year: 2010..For this purpose, the different steps of the viral life cycle will be examined. Moreover, the status of the innate immune response in the persistently infected cells will be evaluated. ..