TRIM28 protects TRIM24 from SPOP-mediated degradation and promotes prostate cancer progression
Year: 2018
Type: article
Abstract: TRIM24 is an effector substrate of the E3 ubiquitin ligase adaptor SPOP and becomes stabilized in prostate cancer (PCa) with SPOP mutations. However, how TRIM24 protein is regulated in the vast majority of SPOP-wildtype PCa is unknown. Here we report TRIM28 as a critical upstream regulator of TRIM24. TRIM28 protein interacts with TRIM24 to prevent its ubiquitination and degradation by SPOP. Further, TRIM28 facilitates TRIM24 occupancy on the chromatin and, like TRIM24, augments AR signaling. TRIM28 promotes PCa cell proliferation in vitro and xenograft tumor growth in vivo. Importantly, TRIM28 is upregulated in aggressive PCa and associated with elevated levels of TRIM24 and worse clinical outcome. TRIM24 and AR coactivated gene signature of SPOP-mutant PCa is similarly activated in human PCa with high TRIM28 expression. Taken together, this study provides a novel mechanism to broad TRIM24 protein stabilization and establishes TRIM28 as a promising therapeutic target.
Source: Nature Communications
Authors: Ka-wing Fong, Jonathan C. Zhao, Bing Song, Bin Zheng, Jindan Yu
Language: English
Subfield: Pulmonary and Respiratory Medicine
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $6,990
Awards: G1080240078, Genomics and bioinformatics analysis to understand castration-resistant prostate cancer, G2040153736, TARGETING EZH2 IN CASTRATION-RESISTANT PROSTATE CANCER, G4119534169, G5832509643, G5850682332, ROLE OF C10ORFL12 IN PROSTATE CANCER, G8831759833, G8994183186, G9000087989, G9000223060
OpenAlex ID: W2901276642