TRIM33 drives prostate tumor growth by stabilizing androgen receptor from Skp2-mediated degradation

ABSTRACT: Androgen receptor (AR) is a master transcription factor that drives prostate cancer (PCa) development and progression. Alterations in the expression or activity of AR coregulators significantly impact the outcome of the disease. Using a proteomics approach, we identified the Tripartite Motif Containing 33 (TRIM33) as a novel transcriptional coactivator of AR. We demonstrate that TRIM33 facilitates AR chromatin binding to directly regulate a transcription program that promotes PCa progression. TRIM33 further stabilizes AR by protecting it from Skp2-mediated ubiquitination and proteasomal degradation. We also show that TRIM33 is essential for PCa tumor growth by avoiding cell cycle arrest and apoptosis, and TRIM33 knockdown sensitizes PCa cells to AR antagonists. In clinical analyses, we fin

SUBMITTER: Ms. Mi Chen 

PROVIDER: S-SCDT-EMBOR-2021-53468-T | biostudies-other |

REPOSITORIES: biostudies-other