Target Identification for Differentiation Therapy of Prostate Cancer
Final rept. 1 Feb 2004-31 Jul 2005
JOHNS HOPKINS UNIV BALTIMORE MD SCHOOL OF MEDICINE
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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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