Eickhoff Nils, Janetzko Janina, Padrão Nuno, Gregoricchio Sebastian, Siefert Joseph C, Hoekman Liesbeth, Linder Simon, Bleijerveld Onno, Bergman Andries M, Zwart Wilbert
Division of Oncogenomics, The Netherlands Cancer Institute, Amsterdam, The Netherlands.
Oncode Institute, Utrecht, The Netherlands.
Commun Biol. 2025 Jul 11;8(1):1043. doi: 10.1038/s42003-025-08449-2.
The Androgen Receptor (AR) is a ligand-dependent transcription factor that drives prostate cancer development and progression. Although, a detailed effect on AR biology has been described for a number of interacting proteins, many AR coregulators remain to be characterized in relation to their distinct impact on AR function. Here, we describe TRIM33 as a conserved AR-interactor across multiple prostate cancer cell lines. We observed that TRIM33 and AR share overall chromatin interaction profiles, in which TRIM33 is involved in downstream responsive transcriptomic output. In contrast to prior reports, we show that TRIM33 does not impact AR protein stability, but instead propose a model in which TRIM33 facilitates maximal AR activity by interfering with H2BK120 ubiquitination levels.
雄激素受体（AR）是一种依赖配体的转录因子，它驱动前列腺癌的发生和发展。尽管已经描述了许多相互作用蛋白对AR生物学的详细影响，但许多AR共调节因子对AR功能的独特影响仍有待表征。在这里，我们将TRIM33描述为多种前列腺癌细胞系中保守的AR相互作用蛋白。我们观察到TRIM33和AR具有整体染色质相互作用图谱，其中TRIM33参与下游反应性转录组输出。与先前的报道相反，我们表明TRIM33不影响AR蛋白稳定性，而是提出了一个模型，即TRIM33通过干扰H2BK120泛素化水平促进AR的最大活性。
