Michael Ohh

Summary

Affiliation: University of Toronto
Country: Canada

Publications

  1. ncbi Human HIF-3alpha4 is a dominant-negative regulator of HIF-1 and is down-regulated in renal cell carcinoma
    Mindy A Maynard
    Department of Laboratory Medicine and Pathobiology, Faculty of Medicine, University of Toronto, Toronto, Ontario, Canada
    FASEB J 19:1396-406. 2005
  2. ncbi Characterization of a von Hippel Lindau pathway involved in extracellular matrix remodeling, cell invasion, and angiogenesis
    Ghada Kurban
    McGill Cancer Center and Department of Biochemistry, McGill University, 3655 Promenade Sir William Osler, Montreal, Quebec H3G 1Y6, Canada
    Cancer Res 66:1313-9. 2006
  3. ncbi pVHL's kryptonite: E2-EPF UCP
    Michael Ohh
    Department of Laboratory Medicine and Pathobiology, University of Toronto, 1 King s College Circle, Toronto, Ontario M5S 1A8, Canada
    Cancer Cell 10:95-7. 2006
  4. pmc Loss of VHL confers hypoxia-inducible factor (HIF)-dependent resistance to vesicular stomatitis virus: role of HIF in antiviral response
    Irene I L Hwang
    Department of Laboratory Medicine and Pathobiology, University of Toronto, 1 King s College Circle, Toronto, Ontario M5S 1A8, Canada
    J Virol 80:10712-23. 2006
  5. pmc Role of the NEDD8 modification of Cul2 in the sequential activation of ECV complex
    Roxana I Sufan
    Department of Laboratory Medicine and Pathobiology, University of Toronto, 1 King s College Circle, Toronto, Ontario, Canada M5S 1A8
    Neoplasia 8:956-63. 2006
  6. pmc Oxygen-independent degradation of HIF-alpha via bioengineered VHL tumour suppressor complex
    Roxana I Sufan
    Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON, Canada
    EMBO Mol Med 1:66-78. 2009
  7. pmc SOCS-1 Mediates Ubiquitylation and Degradation of GM-CSF Receptor
    Severa Bunda
    Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario, Canada
    PLoS ONE 8:e76370. 2013
  8. ncbi Molecular targets from VHL studies into the oxygen-sensing pathway
    M A Maynard
    Department of Laboratory Medicine and Pathobiology, Faculty of Medicine, University of Toronto, 1 King s College Circle, Toronto, Ontario, M5S 1A8, Canada
    Curr Cancer Drug Targets 5:345-56. 2005
  9. pmc Ubiquitin pathway in VHL cancer syndrome
    Michael Ohh
    Department of Laboratory Medicine and Pathobiology, University of Toronto, 1 King s College Circle, Toronto, Ontario, Canada
    Neoplasia 8:623-9. 2006
  10. pmc pVHL modification by NEDD8 is required for fibronectin matrix assembly and suppression of tumor development
    Natalie H Stickle
    Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario M5S 1A8, Canada
    Mol Cell Biol 24:3251-61. 2004

Collaborators

Detail Information

Publications48

  1. ncbi Human HIF-3alpha4 is a dominant-negative regulator of HIF-1 and is down-regulated in renal cell carcinoma
    Mindy A Maynard
    Department of Laboratory Medicine and Pathobiology, Faculty of Medicine, University of Toronto, Toronto, Ontario, Canada
    FASEB J 19:1396-406. 2005
    ..These results demonstrate an important dominant-negative regulation of HIF-1-mediated gene transcription by HIF-3alpha4 in vivo and underscore its potential significance in renal epithelial oncogenesis...
  2. ncbi Characterization of a von Hippel Lindau pathway involved in extracellular matrix remodeling, cell invasion, and angiogenesis
    Ghada Kurban
    McGill Cancer Center and Department of Biochemistry, McGill University, 3655 Promenade Sir William Osler, Montreal, Quebec H3G 1Y6, Canada
    Cancer Res 66:1313-9. 2006
    ..We conclude that loss of ECM integrity could promote and maintain tumor angiogenesis by providing a route for blood vessels to infiltrate tumors...
  3. ncbi pVHL's kryptonite: E2-EPF UCP
    Michael Ohh
    Department of Laboratory Medicine and Pathobiology, University of Toronto, 1 King s College Circle, Toronto, Ontario M5S 1A8, Canada
    Cancer Cell 10:95-7. 2006
    ....
  4. pmc Loss of VHL confers hypoxia-inducible factor (HIF)-dependent resistance to vesicular stomatitis virus: role of HIF in antiviral response
    Irene I L Hwang
    Department of Laboratory Medicine and Pathobiology, University of Toronto, 1 King s College Circle, Toronto, Ontario M5S 1A8, Canada
    J Virol 80:10712-23. 2006
    ..These results reveal a previously unrecognized role of HIF in the antiviral response by promoting the expression of the IFN-beta gene and other genes with antiviral activity upon viral infection...
  5. pmc Role of the NEDD8 modification of Cul2 in the sequential activation of ECV complex
    Roxana I Sufan
    Department of Laboratory Medicine and Pathobiology, University of Toronto, 1 King s College Circle, Toronto, Ontario, Canada M5S 1A8
    Neoplasia 8:956-63. 2006
    ..These events establish a central role for the neddylation of Cul2 in a previously unrecognized, temporally coordinated activation of ECV with the recruitment of its substrate HIFalpha...
  6. pmc Oxygen-independent degradation of HIF-alpha via bioengineered VHL tumour suppressor complex
    Roxana I Sufan
    Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON, Canada
    EMBO Mol Med 1:66-78. 2009
    ..These findings introduce the concept and feasibility of 'bio-tailored' enzymes in the treatment of HIF-overexpressing tumours...
  7. pmc SOCS-1 Mediates Ubiquitylation and Degradation of GM-CSF Receptor
    Severa Bunda
    Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario, Canada
    PLoS ONE 8:e76370. 2013
    ....
  8. ncbi Molecular targets from VHL studies into the oxygen-sensing pathway
    M A Maynard
    Department of Laboratory Medicine and Pathobiology, Faculty of Medicine, University of Toronto, 1 King s College Circle, Toronto, Ontario, M5S 1A8, Canada
    Curr Cancer Drug Targets 5:345-56. 2005
    ....
  9. pmc Ubiquitin pathway in VHL cancer syndrome
    Michael Ohh
    Department of Laboratory Medicine and Pathobiology, University of Toronto, 1 King s College Circle, Toronto, Ontario, Canada
    Neoplasia 8:623-9. 2006
    ..This review will examine recent progress in our understanding of the molecular mechanisms governing the function of ECV and the significance of consequential regulation of HIF in oncogenesis...
  10. pmc pVHL modification by NEDD8 is required for fibronectin matrix assembly and suppression of tumor development
    Natalie H Stickle
    Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario M5S 1A8, Canada
    Mol Cell Biol 24:3251-61. 2004
    ..These results suggest that NEDD8 modification of pVHL plays an important role in fibronectin matrix assembly and that in the absence of such regulation, an intact HIF pathway is insufficient to prevent VHL-associated tumorigenesis...
  11. pmc NEDD8 acts as a 'molecular switch' defining the functional selectivity of VHL
    Ryan C Russell
    Department of Laboratory Medicine and Pathobiology, University of Toronto, 1 King s College Circle, Toronto, Ontario, Canada M5S 1A8
    EMBO Rep 9:486-91. 2008
    ..These findings provide the first mechanistic step in defining the functional selectivity of VHL and explain a previously unrecognized function of NEDD8...
  12. ncbi Nuclear E-cadherin and VHL immunoreactivity are prognostic indicators of clear-cell renal cell carcinoma
    Michelle L Gervais
    Department of Laboratory Medicine and Pathobiology, Faculty of Medicine, University of Toronto, Toronto, ON, Canada
    Lab Invest 87:1252-64. 2007
    ..These findings provide the first evidence of aberrant nuclear localization of E-cadherin in CC-RCC harboring VHL mutations, and suggest potential prognostic value of VHL and E-cadherin in CC-RCC...
  13. pmc DCNL1 functions as a substrate sensor and activator of cullin 2-RING ligase
    Pardeep Heir
    Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario, Canada
    Mol Cell Biol 33:1621-31. 2013
    ..These findings support a model in which substrate engagement prompts DCNL1 recruitment that facilitates the initiation of CUL2 neddylation and define DCNL1 as a "substrate sensor switch" for ECV activation...
  14. ncbi Dominant-negative HIF-3 alpha 4 suppresses VHL-null renal cell carcinoma progression
    Mindy A Maynard
    Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario, Canada
    Cell Cycle 6:2810-6. 2007
    ....
  15. ncbi Mdm2-mediated NEDD8 modification of TAp73 regulates its transactivation function
    Ian R Watson
    Cancer Research Program and Division of Haematology Oncology, Hospital for Sick Children, Toronto, Ontario M5G 1X8, Canada
    J Biol Chem 281:34096-103. 2006
    ....
  16. pmc VHL promotes E2 box-dependent E-cadherin transcription by HIF-mediated regulation of SIP1 and snail
    Andrew J Evans
    Department of Laboratory Medicine and Pathobiology, Faculty of Medicine, University of Toronto, 1 King s College Circle, Toronto, Ontario M5S 1A8, Canada
    Mol Cell Biol 27:157-69. 2007
    ..These findings reveal a critical HIF-dependent molecular pathway connecting VHL, an established "gatekeeper" of the renal epithelium, with a major epithelial tumor suppressor, E-cadherin...
  17. pmc Hypoxia promotes ligand-independent EGF receptor signaling via hypoxia-inducible factor-mediated upregulation of caveolin-1
    Yi Wang
    Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON, Canada M5S 1A8
    Proc Natl Acad Sci U S A 109:4892-7. 2012
    ....
  18. ncbi Molecular cloning and characterization of the von Hippel-Lindau-like protein
    Heng Qi
    Department of Laboratory Medicine and Pathobiology, University of Toronto, 1 King s College Circle, Toronto, Ontario M5S 1A8, Canada
    Mol Cancer Res 2:43-52. 2004
    ..These results taken together indicate that VLP functions as a dominant-negative VHL to serve as a protector of HIFalpha...
  19. pmc Oncolytic targeting of renal cell carcinoma via encephalomyocarditis virus
    Frederik C Roos
    Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario, Canada
    EMBO Mol Med 2:275-88. 2010
    ..These findings provide compelling pre-clinical evidence for the usage of EMCV in the treatment of CCRCC and potentially other tumours with elevated HIF/NF-kappaB-survival signature...
  20. ncbi Von Hippel-Lindau tumor suppressor protein and hypoxia-inducible factor in kidney cancer
    Mindy A Maynard
    Department of Laboratory Medicine and Pathobiology, Faculty of Medicine, University of Toronto, Toronto, Ont, Canada
    Am J Nephrol 24:1-13. 2004
    ..Our current molecular understanding of the roles of HIF and pVHL in the development of VHL-associated clear-cell renal cell carcinoma (CC-RCC) is the focus of this review...
  21. pmc Loss of JAK2 regulation via a heterodimeric VHL-SOCS1 E3 ubiquitin ligase underlies Chuvash polycythemia
    Ryan C Russell
    Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario, Canada
    Nat Med 17:845-53. 2011
    ..These results show that VHL is a SOCS1-cooperative negative regulator of JAK2 and provide biochemical and preclinical support for JAK2-targeted therapy in individuals with Chuvash polycythemia...
  22. ncbi The role of von Hippel-Lindau tumor suppressor protein and hypoxia in renal clear cell carcinoma
    Roxana I Sufan
    Department of Laboratory Medicine and Pathobiology, Faculty of Medicine, University of Toronto, Toronto, ON, Canada M5S 1A8
    Am J Physiol Renal Physiol 287:F1-6. 2004
    ..Recent insights into the molecular mechanisms regulating the function of pVHL, and thereby HIF, in the context of kidney cancer are the focus of this review...
  23. pmc Deregulation of E2-EPF ubiquitin carrier protein in papillary renal cell carcinoma
    Frederik C Roos
    Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario, Canada
    Am J Pathol 178:853-60. 2011
    ..These findings reveal deregulation of the oxygen-sensing pathway impinging on the positive feedback mechanism of HIF1-mediated regulation of E2-EPF in PRCC...
  24. doi Inhibition of SRC corrects GM-CSF hypersensitivity that underlies juvenile myelomonocytic leukemia
    Severa Bunda
    Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario, Canada
    Cancer Res 73:2540-50. 2013
    ..These findings reveal Src kinase as a critical oncogenic driver underlying JMML...
  25. pmc The updated biology of hypoxia-inducible factor
    Samantha N Greer
    Department of Laboratory Medicine and Pathobiology, University of Toronto, 1 King s College Circle, Toronto, Ontario, Canada
    EMBO J 31:2448-60. 2012
    ....
  26. ncbi Multiple splice variants of the human HIF-3 alpha locus are targets of the von Hippel-Lindau E3 ubiquitin ligase complex
    Mindy A Maynard
    Department of Laboratory Medicine and Pathobiology, Faculty of Medicine, University of Toronto, Toronto, Ontario M5S 1A8, Canada
    J Biol Chem 278:11032-40. 2003
    ..These results demonstrate additional targets of the pVHL complex and suggest a growing complexity in the regulation of hypoxia-inducible genes by the HIF family of transcription factors...
  27. doi NEDD8 pathways in cancer, Sine Quibus Non
    Ian R Watson
    Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON, Canada
    Cancer Cell 19:168-76. 2011
    ....
  28. pmc Suppression of hypoxia-inducible factor 2alpha restores p53 activity via Hdm2 and reverses chemoresistance of renal carcinoma cells
    Andrew M Roberts
    Department of Laboratory Medicine, Faculty of Medicine, University of Toronto, Toronto, Ontario, Canada
    Cancer Res 69:9056-64. 2009
    ..These findings unveil a mechanistic link between HIF2alpha and p53 and provide a rationale for combining Hdm2 antagonists with chemotherapy for the treatment of CCRCC...
  29. ncbi Expression of p53 in renal carcinoma cells is independent of pVHL
    Natalie H Stickle
    Department of Laboratory Medicine and Pathobiology, University of Toronto, 1 King s College Circle, Toronto, Ont, Canada M5S 1A8
    Mutat Res 578:23-32. 2005
    ..These results suggest that the expression of p53 in RCC cells is independent of pVHL...
  30. ncbi The von Hippel-Lindau tumor suppressor protein sensitizes renal cell carcinoma cells to tumor necrosis factor-induced cytotoxicity by suppressing the nuclear factor-kappaB-dependent antiapoptotic pathway
    Heng Qi
    Department of Laboratory Medicine and Pathobiology, Faculty of Medicine, University of Toronto, Toronto, Ontario, M5S 1A8 Canada
    Cancer Res 63:7076-80. 2003
    ....
  31. doi Oxygen-mediated endocytosis in cancer
    Yi Wang
    Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON, Canada
    J Cell Mol Med 14:496-503. 2010
    ..These recent discoveries underscore the emergence of endocytosis as an important hypoxia-mediated regulatory process in cancer...
  32. ncbi The role of VHL in the regulation of E-cadherin: a new connection in an old pathway
    Ryan C Russell
    Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario, Canada
    Cell Cycle 6:56-9. 2007
    ..This review highlights recent discoveries uncovering the transcriptional regulation of E-cadherin, a homophilic cell adhesion molecule with anti-invasive properties in numerous epithelial-derived cancers, via the VHL-HIF pathway...
  33. pmc Functional importance of Dicer protein in the adaptive cellular response to hypoxia
    J J David Ho
    Department of Medical Biophysics, University of Toronto, Toronto, Ontario M5B 1W8, Canada
    J Biol Chem 287:29003-20. 2012
    ....
  34. ncbi Regulation of endocytosis via the oxygen-sensing pathway
    Yi Wang
    Department of Laboratory Medicine and Pathobiology, St Michael s Hospital, University of Toronto, 1 King s College Circle, Toronto, Ontario M5S 1A8, Canada
    Nat Med 15:319-24. 2009
    ....
  35. pmc SATB2 augments ΔNp63α in head and neck squamous cell carcinoma
    Jacky Chung
    Department of Molecular Genetics, University of Toronto, Cell Biology Program, Hospital for Sick Children Research Institute, Department of Paediatrics, 555 University Avenue, Toronto, Ontario, M5G 1L7, Canada
    EMBO Rep 11:777-83. 2010
    ..These findings unveil SATB2 as a pivotal modulator of ΔNp63α that governs HNSCC cell survival...
  36. doi Transcriptional regulation of genes via hypoxia-inducible factor
    Olga Roche
    Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON, Canada
    Methods Mol Biol 809:189-99. 2012
    ..Here, we describe classical experimental approaches to demonstrate and validate HIF-responsive transcriptional regulation of genes...
  37. ncbi Hypoxia-inducible expression of a natural cis-antisense transcript inhibits endothelial nitric-oxide synthase
    Jason E Fish
    Department of Medical Biophysics, St Michael s Hospital, University of Toronto, Toronto, Ontario M5S 1A8, Canada
    J Biol Chem 282:15652-66. 2007
    ....
  38. ncbi Beyond the hypoxia-inducible factor-centric tumour suppressor model of von Hippel-Lindau
    Andrew M Roberts
    Department of Laboratory Medicine and Pathobiology, University of Toronto, Ontario, Canada
    Curr Opin Oncol 20:83-9. 2008
    ..To provide an overview of the recent advances in the understanding of the molecular mechanisms governing the tumour suppressor functions of the von Hippel-Lindau protein...
  39. ncbi Homotypic association between tumour-associated VHL proteins leads to the restoration of HIF pathway
    J Chung
    Department of Laboratory Medicine and Pathobiology, University of Toronto, Ontario, Canada
    Oncogene 25:3079-83. 2006
    ....
  40. ncbi The role of hypoxia-inducible factors in cancer
    M A Maynard
    Department of Laboratory Medicine and Pathobiology, University of Toronto, 1 King s College Circle, M5S1A8, Toronto, Ontario, Canada
    Cell Mol Life Sci 64:2170-80. 2007
    ....
  41. doi Chemotherapy induces NEDP1-mediated destabilization of MDM2
    I R Watson
    Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario, Canada
    Oncogene 29:297-304. 2010
    ..These findings unveil the regulation of MDM2 stability through NEDP1 as a common molecular determinant governing chemotherapy-induced p53-dependent cell death...
  42. pmc Diverse effects of mutations in exon II of the von Hippel-Lindau (VHL) tumor suppressor gene on the interaction of pVHL with the cytosolic chaperonin and pVHL-dependent ubiquitin ligase activity
    William J Hansen
    Surgical Research Laboratory, San Francisco General Hospital, 1001 Potrero Ave, San Francisco, CA 94110, USA
    Mol Cell Biol 22:1947-60. 2002
    ....
  43. ncbi VHL and kidney cancer
    Michael Ohh
    Dana Farber Cancer Institute, Boston, MA, USA
    Methods Mol Biol 222:167-83. 2003
  44. pmc Somatic pairing of chromosome 19 in renal oncocytoma is associated with deregulated EGLN2-mediated [corrected] oxygen-sensing response
    Julie M Koeman
    Laboratory of Germline Modification and Cytogenetics, Van Andel Research Institute, Grand Rapids, Michigan, United States of America
    PLoS Genet 4:e1000176. 2008
    ..The identification of EGLN2 as a significantly deregulated gene that maps within the paired chromosome region directly implicates defects in the oxygen-sensing network to the biology of renal oncocytoma...
  45. ncbi Tumor suppression by the von Hippel-Lindau protein requires phosphorylation of the acidic domain
    Martijn P Lolkema
    Department of Medical Oncology, University Medical Center Utrecht, Heidelberglaan 100, 3584 CX Utrecht, The Netherlands
    J Biol Chem 280:22205-11. 2005
    ..We propose that phosphorylation of the acidic domain plays a role in the regulation of proper fibronectin matrix deposition and that this may be relevant for the development of VHL-associated malignancies...
  46. pmc An intact NEDD8 pathway is required for Cullin-dependent ubiquitylation in mammalian cells
    Michael Ohh
    Department of Adult Oncology, Dana Farber Cancer Institute and Brigham and Women s Hospital, Harvard Medical School, Boston, MA 02115, USA
    EMBO Rep 3:177-82. 2002
    ..Thus, neddylation regulates the activity of two specific subclasses of mammalian ubiquitin ligases...
  47. ncbi von Hippel-Lindau tumor suppressor protein regulates the assembly of intercellular junctions in renal cancer cells through hypoxia-inducible factor-independent mechanisms
    Maria J Calzada
    Servicio de Inmunologia, Hospital de la Princesa, Departamento de Medicina, Universidad Autonoma de Madrid, Diego de Leon 62, 28006 Madrid, Spain
    Cancer Res 66:1553-60. 2006
    ..In summary, we show that VHL inactivation in RCC cells disrupts intercellular junctions and cell shape through HIF-independent events, supporting the concept that VHL has additional functions beside its role in the regulation of HIF...