Target Identification for Differentiation Therapy of Prostate Cancer

Abstract

Work carried out under this grant showed that hyperphosphorylated Rb interacts with pp32 but not with the closely related proteins pp32r1 and pp32r2. Furthermore, pp32-Rb interaction inhibits the apoptotic activity of pp32 and stimulates proliferation. These results suggest a mechanism whereby cancer cells gain both a proliferative and survival advantage when Rb is inactivated by hyperphosphorylation. Further extension of these studies showed that pp32 increases androgen receptormediated transcription and the retinoblastoma protein modulates this activity. Furthermore, the results suggest that pp32 and the retinoblastoma protein may be part of a multiprotein complex that coordinately regulates nuclear receptor-mediated transcription and mRNA processing. Together, these findings indicate that the pp32-Rb interaction could serve as a drug target in prostate cancer.

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Document Details

Document Type
Technical Report
Publication Date
Aug 01, 2005
Accession Number
ADA508627

Entities

People

  • Gary R. Pasternack

Organizations

  • Johns Hopkins University

Tags

DTIC Thesaurus Topics

  • Amino Acids
  • Androgen Receptors
  • Biomedical And Dental Materials
  • Cell Line
  • Cell Physiological Processes
  • Cells
  • Chemical Synthesis
  • Chemistry
  • Deoxyribonucleic Acids
  • Hormones
  • Indicator Dyes
  • Molecular Biology
  • Multiprotein Complexes
  • Neoplasms
  • Prostate Cancer
  • Proteins
  • Proteomics

Fields of Study

  • Biology

Readers

  • Molecular Biology and Genetics