Andrei V Gudkov

Summary

Affiliation: Cleveland Clinic Foundation
Country: USA

Publications

  1. pmc Regulation of NF-kappaB by NSD1/FBXL11-dependent reversible lysine methylation of p65
    Tao Lu
    Department of Molecular Genetics, Lerner Research Institute, Cleveland Clinic Foundation, Cleveland, OH 44195, USA
    Proc Natl Acad Sci U S A 107:46-51. 2010
  2. ncbi request reprint The role of p53 in determining sensitivity to radiotherapy
    Andrei V Gudkov
    Department of Molecular Biology, NC20, Lerner Research Institute, Cleveland Clinic Foundation, 9500 Euclid Avenue, Cleveland, Ohio 44195, USA
    Nat Rev Cancer 3:117-29. 2003
  3. pmc Small molecules that reactivate p53 in renal cell carcinoma reveal a NF-kappaB-dependent mechanism of p53 suppression in tumors
    Katerina V Gurova
    Department of Molecular Genetics, The Cleveland Clinic Foundation, Cleveland, OH 44195, USA
    Proc Natl Acad Sci U S A 102:17448-53. 2005
  4. ncbi request reprint Prospective therapeutic applications of p53 inhibitors
    Andrei V Gudkov
    Department of Molecular Genetics, Lerner Research Institute, The Cleveland Clinic Foundation, Cleveland, OH 44195, USA
    Biochem Biophys Res Commun 331:726-36. 2005
  5. ncbi request reprint Inhibition of p53 response in tumor stroma improves efficacy of anticancer treatment by increasing antiangiogenic effects of chemotherapy and radiotherapy in mice
    Lyudmila G Burdelya
    Department of Molecular Genetics, Lerner Research Institute, The Cleveland Clinic Foundation, Cleveland, OH 44195, USA
    Cancer Res 66:9356-61. 2006
  6. ncbi request reprint Melanoma cells can tolerate high levels of transcriptionally active endogenous p53 but are sensitive to retrovirus-transduced p53
    Julia V Kichina
    Department of Molecular Biology, Lerner Research Institute, Cleveland Clinic Foundation, 9500 Euclid Avenue, Cleveland, OH 44195, USA
    Oncogene 22:4911-7. 2003
  7. pmc Validation-based insertional mutagenesis identifies lysine demethylase FBXL11 as a negative regulator of NFkappaB
    Tao Lu
    Department of Molecular Genetics, Lerner Research Institute, Cleveland Clinic Foundation, Cleveland, OH 44195, USA
    Proc Natl Acad Sci U S A 106:16339-44. 2009
  8. ncbi request reprint The ability of protein tyrosine phosphatase SHP-1 to suppress NFkappaB can be inhibited by dominant negative mutant of SIRPalpha
    Nickolay Neznanov
    Department of Virology, Lerner Research Institute, Cleveland Clinic Foundation, Cleveland, Ohio 44195, USA
    DNA Cell Biol 23:175-82. 2004
  9. ncbi request reprint p53 is a suppressor of inflammatory response in mice
    Elena A Komarova
    Department of Molecular Biology, Lerner Research Institute, Cleveland Clinic Foundation, Cleveland, Ohio 44195, USA
    FASEB J 19:1030-2. 2005
  10. pmc Different effect of proteasome inhibition on vesicular stomatitis virus and poliovirus replication
    Nickolay Neznanov
    Department of Molecular Genetics, Lerner Research Institute, Cleveland Clinic Foundation, Cleveland, Ohio, United States of America
    PLoS ONE 3:e1887. 2008

Research Grants

Collaborators

Detail Information

Publications47

  1. pmc Regulation of NF-kappaB by NSD1/FBXL11-dependent reversible lysine methylation of p65
    Tao Lu
    Department of Molecular Genetics, Lerner Research Institute, Cleveland Clinic Foundation, Cleveland, OH 44195, USA
    Proc Natl Acad Sci U S A 107:46-51. 2010
    ..We conclude that reversible lysine methylation of NF-kappaB is an important element in the complex regulation of this key transcription factor...
  2. ncbi request reprint The role of p53 in determining sensitivity to radiotherapy
    Andrei V Gudkov
    Department of Molecular Biology, NC20, Lerner Research Institute, Cleveland Clinic Foundation, 9500 Euclid Avenue, Cleveland, Ohio 44195, USA
    Nat Rev Cancer 3:117-29. 2003
    ..One of the key molecules involved in a cell's response to IR is p53. Understanding these mechanisms indicates new rational approaches to improving cancer treatment by IR...
  3. pmc Small molecules that reactivate p53 in renal cell carcinoma reveal a NF-kappaB-dependent mechanism of p53 suppression in tumors
    Katerina V Gurova
    Department of Molecular Genetics, The Cleveland Clinic Foundation, Cleveland, OH 44195, USA
    Proc Natl Acad Sci U S A 102:17448-53. 2005
    ....
  4. ncbi request reprint Prospective therapeutic applications of p53 inhibitors
    Andrei V Gudkov
    Department of Molecular Genetics, Lerner Research Institute, The Cleveland Clinic Foundation, Cleveland, OH 44195, USA
    Biochem Biophys Res Commun 331:726-36. 2005
    ....
  5. ncbi request reprint Inhibition of p53 response in tumor stroma improves efficacy of anticancer treatment by increasing antiangiogenic effects of chemotherapy and radiotherapy in mice
    Lyudmila G Burdelya
    Department of Molecular Genetics, Lerner Research Institute, The Cleveland Clinic Foundation, Cleveland, OH 44195, USA
    Cancer Res 66:9356-61. 2006
    ..Thus, reversible pharmacologic suppression of p53 may be a viable approach to improving anticancer treatment via an enhanced antiangiogenic effect of chemotherapy and radiotherapy...
  6. ncbi request reprint Melanoma cells can tolerate high levels of transcriptionally active endogenous p53 but are sensitive to retrovirus-transduced p53
    Julia V Kichina
    Department of Molecular Biology, Lerner Research Institute, Cleveland Clinic Foundation, 9500 Euclid Avenue, Cleveland, OH 44195, USA
    Oncogene 22:4911-7. 2003
    ..Hence, the p53 pathway in malignant melanomas can be considered for pharmacological targeting and anticancer gene therapy...
  7. pmc Validation-based insertional mutagenesis identifies lysine demethylase FBXL11 as a negative regulator of NFkappaB
    Tao Lu
    Department of Molecular Genetics, Lerner Research Institute, Cleveland Clinic Foundation, Cleveland, OH 44195, USA
    Proc Natl Acad Sci U S A 106:16339-44. 2009
    ..Thus, we have used a powerful tool for mutagenesis of mammalian cells to reveal an aspect of the complex regulation of NFkappaB-dependent signaling...
  8. ncbi request reprint The ability of protein tyrosine phosphatase SHP-1 to suppress NFkappaB can be inhibited by dominant negative mutant of SIRPalpha
    Nickolay Neznanov
    Department of Virology, Lerner Research Institute, Cleveland Clinic Foundation, Cleveland, Ohio 44195, USA
    DNA Cell Biol 23:175-82. 2004
    ..The expression of dominant negative mutant of SIRPalpha has an effect similar to the expression of dominant negative PTP SHP-1 in the process of NFkappaB activation...
  9. ncbi request reprint p53 is a suppressor of inflammatory response in mice
    Elena A Komarova
    Department of Molecular Biology, Lerner Research Institute, Cleveland Clinic Foundation, Cleveland, Ohio 44195, USA
    FASEB J 19:1030-2. 2005
    ....
  10. pmc Different effect of proteasome inhibition on vesicular stomatitis virus and poliovirus replication
    Nickolay Neznanov
    Department of Molecular Genetics, Lerner Research Institute, Cleveland Clinic Foundation, Cleveland, Ohio, United States of America
    PLoS ONE 3:e1887. 2008
    ..To our knowledge, this is the first study that connects the effect of stress induced by proteasome inhibition with the efficiency of viral infection...
  11. pmc A systematic search for downstream mediators of tumor suppressor function of p53 reveals a major role of BTG2 in suppression of Ras-induced transformation
    Alexander D Boiko
    Department of Molecular Genetics, Lerner Research Institute, Cleveland Clinic Foundation, Cleveland, Ohio 44195, USA
    Genes Dev 20:236-52. 2006
    ..BTG2 expression was found to be significantly reduced in a large proportion of human kidney and breast carcinomas, suggesting that BTG2 is a tumor suppressor that links p53 and Rb pathways in human tumorigenesis...
  12. ncbi request reprint p53 pathway in renal cell carcinoma is repressed by a dominant mechanism
    Katerina V Gurova
    Department of Molecular Biology, Lerner Research Institute, The Cleveland Clinic Foundation, 9500 Euclid Avenue, Cleveland, OH 44195, USA
    Cancer Res 64:1951-8. 2004
    ..Remarkably, cells of normal kidney epithelium also caused partial p53 repression in cell fusion experiments, suggesting that RCC-specific p53 repression may be based on an unknown dominant mechanism also acting in normal kidney tissue...
  13. ncbi request reprint Levels of HdmX expression dictate the sensitivity of normal and transformed cells to Nutlin-3
    John T Patton
    Department of Molecular Genetics, Lerner Research Institute, Cleveland Clinic Foundation, Ohio 44195, USA
    Cancer Res 66:3169-76. 2006
    ..Our findings establish Hdm2 and HdmX as independent therapeutic targets with respect to reactivating wild-type p53 as a means for cancer therapy...
  14. ncbi request reprint Serologically defined colon cancer antigen 3 is necessary for the presentation of TNF receptor 1 on cell surface
    Nickolay Neznanov
    Department of Molecular Genetics, Lerner Research Institute, Cleveland Clinic Foundation, OH 44195, USA
    DNA Cell Biol 24:777-85. 2005
    ..Based on these results, we presume that SDCCAG3 is important for protein trafficking and presentation of TNFR1 on the cell surface. Therefore, SDCCAG3 can be viewed as a potential target for modulation of TNF response...
  15. pmc BMAL1-dependent circadian oscillation of nuclear CLOCK: posttranslational events induced by dimerization of transcriptional activators of the mammalian clock system
    Roman V Kondratov
    Department of Cancer Biology, Lerner Research Institute, The Cleveland Clinic Foundation, Cleveland, Ohio 44195, USA
    Genes Dev 17:1921-32. 2003
    ..Altogether, these results provide evidence for an additional level of circadian system control, which is based on regulation of transcriptional activity or/and availability of CLOCK/BMAL1 complex...
  16. pmc Prostate cancer cells tolerate a narrow range of androgen receptor expression and activity
    Natalia D Tararova
    Department of Molecular Genetics, Lerner Research Institute, Cleveland Clinic Foundation, Cleveland, Ohio, USA
    Prostate 67:1801-15. 2007
    ..Our objective was to determine the importance of AR signaling for survival and growth of CaP cells, particularly those with a hormone-refractory phenotype...
  17. ncbi request reprint Small-molecule inhibitor of p53 binding to mitochondria protects mice from gamma radiation
    Evguenia Strom
    Cleveland BioLabs, Inc, 11000 Cedar Ave, Cleveland, Ohio 44106, USA
    Nat Chem Biol 2:474-9. 2006
    ..These results indicate that selective inhibition of the mitochondrial branch of the p53 pathway is sufficient for radioprotection in vivo...
  18. ncbi request reprint Apoptosis inhibitor as a suppressor of tumor progression: expression of Bcl-2 eliminates selective advantages for p53-deficient cells in the tumor
    Katerina V Gurova
    Department of Molecular Biology, Lerner Research Institute, Cleveland Clinic Foundation, Cleveland, Ohio 44195, USA
    Cancer Biol Ther 1:39-44. 2002
    ....
  19. pmc Circadian sensitivity to the chemotherapeutic agent cyclophosphamide depends on the functional status of the CLOCK/BMAL1 transactivation complex
    Victoria Y Gorbacheva
    Department of Cancer Biology, Lerner Research Institute, Cleveland Clinic Foundation, Cleveland, OH 44195, USA
    Proc Natl Acad Sci U S A 102:3407-12. 2005
    ..Based on these results, we propose that the CLOCK/BMAL1 transcriptional complex affects the lethality of chemotherapeutic agents by modulating the survival of the target cells necessary for the viability of the organism...
  20. ncbi request reprint Cooperation of two mutant p53 alleles contributes to Fas resistance of prostate carcinoma cells
    Katerina V Gurova
    Department of Molecular Biology, Lerner Research Institute, Cleveland Clinic Foundation, Cleveland, Ohio 44195, USA
    Cancer Res 63:2905-12. 2003
    ..These results indicate that two different p53 mutants that are separately rather weak can cooperate to generate p53 protein with anti-Fas function that is likely to provide additional selective advantages to the tumor...
  21. ncbi request reprint Dual effect of p53 on radiation sensitivity in vivo: p53 promotes hematopoietic injury, but protects from gastro-intestinal syndrome in mice
    Elena A Komarova
    Department of Molecular Biology, Lerner Research Institute, The Cleveland Clinic Foundation, Cleveland, OH 44195, USA
    Oncogene 23:3265-71. 2004
    ....
  22. ncbi request reprint Quinacrine inhibits the epidermal dendritic cell migration initiating T cell-mediated skin inflammation
    Anton V Gorbachev
    Department of Immunology, Cleveland Clinic, Cleveland, OH 44195 0001, USA
    Eur J Immunol 37:2257-67. 2007
    ..These findings reveal a previously unrecognized mechanism of QC-mediated inhibition of inflammation...
  23. pmc Secreted transforming growth factor beta2 activates NF-kappaB, blocks apoptosis, and is essential for the survival of some tumor cells
    Tao Lu
    Department of Molecular Biology, Lerner Research Institute, Cleveland Clinic Foundation, 9500 Euclid Avenue, Cleveland, OH 44195, USA
    Proc Natl Acad Sci U S A 101:7112-7. 2004
    ..These findings identify TGFbeta2 as a potential target for therapeutic strategies to inhibit the growth of tumor cells that depend on constitutively active NF-kappaB, or to sensitize them to treatment with cytotoxic drugs...
  24. ncbi request reprint Quercetinase pirin makes poliovirus replication resistant to flavonoid quercetin
    Nickolay Neznanov
    Department of Molecular Genetics, Lerner Research Institute, Cleveland Clinic Foundation, Cleveland, Ohio 44195, USA
    DNA Cell Biol 27:191-8. 2008
    ..The results suggest that quercetinase activity of pirin determines the resistance of poliovirus infection to quercetin...
  25. ncbi request reprint Proteolytic cleavage of the p65-RelA subunit of NF-kappaB during poliovirus infection
    Nickolay Neznanov
    Department of Molecular Genetics, Lerner Research Institute, The Cleveland Clinic Foundation, Cleveland, Ohio 44195, USA
    J Biol Chem 280:24153-8. 2005
    ....
  26. ncbi request reprint Poliovirus protein 3A binds and inactivates LIS1, causing block of membrane protein trafficking and deregulation of cell division
    Anna A Kondratova
    Department of Molecular Genetics, Lerner Research Institute, The Cleveland Clinic Foundation, Cleveland, Ohio, USA
    Cell Cycle 4:1403-10. 2005
    ....
  27. ncbi request reprint Sensitization of DNA damage-induced apoptosis by the proteasome inhibitor PS-341 is p53 dependent and involves target proteins 14-3-3sigma and survivin
    Susan A J Vaziri
    Experimental Therapeutics Program, Taussig Cancer Center, Cleveland Clinic Foundation, R40, 9500 Euclid Avenue, Cleveland, OH 44195, USA
    Mol Cancer Ther 4:1880-90. 2005
    ..These results provide insights into the mechanisms by which inhibition of proteasome activity modulates DNA damage-induced apoptosis via a p53-dependent pathway...
  28. ncbi request reprint p53 inhibitor pifithrin alpha can suppress heat shock and glucocorticoid signaling pathways
    Elena A Komarova
    Department of Molecular Biology, Lerner Research Institute, Cleveland Clinic Foundation, 9500 Euclid Avenue, Cleveland, OH 44195, USA
    J Biol Chem 278:15465-8. 2003
    ..PFTalpha affected both signaling pathways in a p53-independent manner. These observations suggest that PFTalpha targets some unknown factor that is common for three major signal transduction pathways...
  29. pmc Selection-subtraction approach (SSA): a universal genetic screening technique that enables negative selection
    Aatur D Singhi
    Department of Molecular Biology, Lerner Research Institute, Cleveland Clinic Foundation, Cleveland, OH 44195, USA
    Proc Natl Acad Sci U S A 101:9327-32. 2004
    ....
  30. ncbi request reprint Dangerous habits of a security guard: the two faces of p53 as a drug target
    Andrei V Gudkov
    Department of Molecular Genetics, Lerner Research Institute, Cleveland Clinic, Cleveland, OH, USA
    Hum Mol Genet 16:R67-72. 2007
    ..Here we briefly review specific aspects of this problem and discuss the ways of its pharmacological resolution based on detailed knowledge of molecular mechanisms of p53 regulation and activity...
  31. ncbi request reprint Paradoxical role of apoptosis in tumor progression
    Katerina V Gurova
    Department of Molecular Biology, Lerner Research Institute, Cleveland Clinic Foundation, Cleveland, Ohio 44195, USA
    J Cell Biochem 88:128-37. 2003
    ....
  32. ncbi request reprint Identification of a novel stress-responsive gene Hi95 involved in regulation of cell viability
    Andrei V Budanov
    Department of Molecular Biology, Lerner Research Institute, Cleveland Clinic Foundation, 9500 Euclid Ave, Ohio, OH 44195, USA
    Oncogene 21:6017-31. 2002
    ..Thus, Hi95 gene seems to be involved in complex regulation of cell viability in response to different stress conditions...
  33. ncbi request reprint Unstable receptors disappear from cell surface during poliovirus infection
    Nickolay Neznanov
    Department of Virology, Lerner Research Institute, Cleveland Clinic Foundation, Cleveland, OH 44195, USA
    Med Sci Monit 8:BR391-6. 2002
    ..We suggested that the rate of decrease in receptor presentation on the surface of infected cells might reflect its turnover rate on uninfected cells...
  34. ncbi request reprint Dominant negative form of signal-regulatory protein-alpha (SIRPalpha /SHPS-1) inhibits tumor necrosis factor-mediated apoptosis by activation of NF-kappa B
    Nickolay Neznanov
    Department of Virology, Lerner Research Institute, Cleveland Clinic Foundation, Ohio 44195, USA
    J Biol Chem 278:3809-15. 2003
    ..These data indicate that SIRPalpha/SHPS-1 is involved in negative regulation of NF-kappaB signaling...
  35. ncbi request reprint Genetic suppressor elements in the characterization and identification of tumor suppressor genes
    Igor B Roninson
    Department of Molecular Genetics, University of Illinois, Chicago, USA
    Methods Mol Biol 222:413-36. 2003
  36. pmc Structural basis of TLR5-flagellin recognition and signaling
    Sung Il Yoon
    Department of Molecular Biology, The Scripps Research Institute, La Jolla, CA 92037, USA
    Science 335:859-64. 2012
    ..The proposed signaling mechanism is supported by structure-guided mutagenesis and deletion analyses on CBLB502, a therapeutic protein derived from FliC...
  37. ncbi request reprint Expression of prostate specific antigen (PSA) is negatively regulated by p53
    Katerina V Gurova
    Department of Molecular Biology, Lerner Research Institute, The Cleveland Clinic Foundation, Cleveland, Ohio, OH 44195, USA
    Oncogene 21:153-7. 2002
    ..Thus, PSA is likely to be a tissue specific indicator of transformation-associated p53 suppression in prostate cells. This finding provides a plausible explanation for a frequent increase of PSA levels in advanced prostate cancer...
  38. pmc A TLR5 agonist inhibits acute renal ischemic failure
    Nobuyuki Fukuzawa
    Glickman Urological and Kidney Institute, Cleveland Clinic, Cleveland, OH 44195, USA
    J Immunol 187:3831-9. 2011
    ..Overall, these results indicate the use of TLR5 agonists as mitigators and protectants of acute renal ischemic failure...
  39. pmc Cdk4 disruption renders primary mouse cells resistant to oncogenic transformation, leading to Arf/p53-independent senescence
    Xianghong Zou
    Department of Molecular Genetics, University of Illinois College of Medicine, Chicago, Illinois 60607, USA
    Genes Dev 16:2923-34. 2002
    ..Therefore, Cdk4 is essential for immortalization, and suppression of Cdk4 could be a prospective strategy to recruit cells with inactive Arf/p53 pathway to senescence...
  40. ncbi request reprint Bisindolylmaleimide IX facilitates tumor necrosis factor receptor family-mediated cell death and acts as an inhibitor of transcription
    Oskar W Rokhlin
    Department of Pathology, The University of Iowa, Iowa City, Iowa 52242, USA
    J Biol Chem 277:33213-9. 2002
    ..In summary, these results suggest that Bis IX potentiates TNF receptor family-mediated cell death in part as an inhibitor of transcription...
  41. ncbi request reprint Falkor, a novel cell growth regulator isolated by a functional genetic screen
    Neta Erez
    Department of Molecular Cell Biology, The Weizmann Institute of Science, Rehovot, Israel 76100
    Oncogene 21:6713-21. 2002
    ..elegans protein EGL-9, recently shown to modify the Hypoxia Inducible Factor-1alpha. The homology suggests that these proteins share a functional domain that is conserved among a family of growth regulation proteins...
  42. pmc Functional genetic screening reveals the role of mitochondrial cytochrome b as a mediator of FAS-induced apoptosis
    Andrei P Komarov
    Department of Cell Stress Biology, Roswell Park Cancer Institute, Buffalo, NY 14263, USA
    Proc Natl Acad Sci U S A 105:14453-8. 2008
    ..These results reveal a cytochrome c-independent branch of FAS-induced apoptosis involving cleavage and cytoplasmic release of mitochondrial Cyt b...
  43. doi request reprint An agonist of toll-like receptor 5 has radioprotective activity in mouse and primate models
    Lyudmila G Burdelya
    Department of Cell Stress Biology, Roswell Park Cancer Institute, Buffalo, NY 14263, USA
    Science 320:226-30. 2008
    ..CBLB502 also showed radioprotective activity in lethally irradiated rhesus monkeys. Thus, TLR5 agonists could potentially improve the therapeutic index of cancer radiotherapy and serve as biological protectants in radiation emergencies...
  44. ncbi request reprint Cancer drug discovery: the wisdom of imprecision
    Andrei V Gudkov
    Nat Med 10:1298-9. 2004
  45. ncbi request reprint Identification of new drug sensitivity genes using genetic suppressor elements: protein arginine N-methyltransferase mediates cell sensitivity to DNA-damaging agents
    Laurent Gros
    Centre National de la Recherche Scientifique UMR 8532, Institut Gustave Roussy, 94805 Villejuif, France
    Cancer Res 63:164-71. 2003
    ..Our data indicate that down-regulation of these enzymes in the GSE-expressing cells would alter one or several steps downstream of the drug-target interaction in the drug-response pathway...
  46. ncbi request reprint p53 determines multidrug sensitivity of childhood neuroblastoma
    Chengyuan Xue
    Children s Cancer Institute Australia for Medical Research, Randwick, New South Wales, Australia
    Cancer Res 67:10351-60. 2007
    ....
  47. pmc Keratinocyte growth factor (KGF) enhances postnatal T-cell development via enhancements in proliferation and function of thymic epithelial cells
    Simona W Rossi
    Laboratory of Pediatric Immunology, Center for Biomedicine, Department of Clinical Biological Sciences, University of Basel, Mattenstrasse 28, 4058 Basel, Switzerland
    Blood 109:3803-11. 2007
    ..Signaling via the canonical BMP pathway is critical for the KGF effects. Taken together, these data provide new insights into the mechanism(s) of action of exogenous KGF on TEC function and thymopoiesis...

Research Grants5

  1. STRESS INDUCED BYSTANDER EFFECT IN CANCER TREATMENT
    Andrei Gudkov; Fiscal Year: 2004
    ..abstract_text> ..
  2. Protecting immune system by modulators of p53 and NF-kB
    Andrei Gudkov; Fiscal Year: 2005
    ..abstract_text> ..
  3. ISSA: novel functional approach to cancer-related genes
    Andrei Gudkov; Fiscal Year: 2006
    ....
  4. GENETIC ELEMENTS TRANSFORMING MOUSE FIBROBLASTS
    Andrei Gudkov; Fiscal Year: 2007
    ..The success of the proposed study will indicate development of a powerful target discovery tool that will be applicable for ACTT identification in other types of cancer. ..
  5. Diagnostic Therapeutic Targets in Prostate Cancer
    Andrei Gudkov; Fiscal Year: 2007
    ....