TRIM33 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 find TRIM33 upregulated in multiple PCa patient cohorts. Finally, we uncover an AR-TRIM33-coactivated gene signature highly expressed in PCa tumors and predict disease recurrence. Overall, our results reveal that TRIM33 is an oncogenic AR coactivator in PCa and a potential therapeutic target for PCa treatment.
Mesh Terms:
Cell Line, Tumor, Gene Expression Regulation, Neoplastic, Humans, Male, Neoplasm Recurrence, Local, Prostatic Neoplasms, Receptors, Androgen, S-Phase Kinase-Associated Proteins, Transcription Factors
EMBO Rep
Date: Dec. 03, 2021
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