biostudies-literatureChen MUniversidade de Macaue53468https://www.ebi.ac.uk/biostudies/studies/S-EPMC9346471biostudies-literatureUnknown23(8)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 finEMBO reportsTRIM33 drives prostate tumor growth by stabilizing androgen receptor from Skp2-mediated degradation.PMC9346471MYRG2020‐00100‐FHSMYRG2018‐00033‐FHSNarwade NZheng YTang AHNLei KMKChen MCheung ELingadahalli SLiu SZhao ZLu QPoon TCWfalseTRIM33 drives prostate tumor growth by stabilizing androgen receptor from Skp2-mediated degradation.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 fin2022-01-01T00:00:00Z2022 Aug2026-07-14T16:42:17.671Z2025-04-21T22:12:29.063ZS-EPMC93464713578541410.15252/embr.202153468