Identification and Characterization of Post-Translational Modifications on EAF1 and EAF2 in Prostate Cancer

Abstract

Abstract : The original project for the grant was to determine if an observed modification of EAF1 and EAF2 altered how EAF2 is regulated in the normal prostate and in prostate cancer. However, co-immunoprecipitation results showed the modification was a covalent dimerization. The project then shifted to determining how the tumor suppressor ELL-associated factor 2 (EAF2) interacts Fork-head box protein A1 and what the ramifications of that interaction would be. Work on specific aim 1; determine how FOXA1 interacts with EAF2, revealed over-expressed FOXA1 binds to EAF2, EAF2 binds to the N-terminus and C-terminus of FOXA1, and over-expression of FOXA1 and EAF2 reduces FOXA1 and EAF2 protein levels, but it remains unknown if over-expression of FOXA1 and EAF2 affects FOXA1 and EAF2 protein stability. Work on specific aim 2; determine the effect of EAF2 on FOXA1-mediated transcription and on FOXA1-mediated cell growth and survival, revealed that loss of EAF2 reduces PSA protein and mRNA levels and increases FOXA1 protein levels, over-expression of FOXA1 reduces PSA-promoter activity, and over-expression of FOXA1 and EAF2 results in an intermediary level of cell survival and proliferation, compared to FOXA1 alone which promoted cell growth and survival and EAF2 alone which promoted cell death. This project led to a dissertation and a PhD.