TRIM28 represses renal cell carcinoma cell proliferation by inhibiting TFE3/KDM6A-regulated autophagy.

ABSTRACT: Autophagy plays a pivotal role in physiology and pathophysiology, including cancer. Mechanisms of autophagy dysregulation in cancer remain elusive. Loss of function of TRIM28, a multifunction protein, is seen in familial kidney malignancy, but the mechanism by which TRIM28 contributes to the etiology of kidney malignancy is unclear. In this study, we show TRIM28 retards kidney cancer cell proliferation through inhibiting autophagy. Mechanistically, we find TRIM28 promotes ubiquitination and proteasome-mediated degradation of transcription factor TFE3, which is critical for autophagic gene expression. Genetic activation of TFE3 due to gene fusion is known to cause human kidney malignancy, but whether and how transcription activation by TFE3 involves chromatin changes is unclear. Here, we fi

SUBMITTER: Song T 

PROVIDER: S-EPMC10141522 | biostudies-literature | 2023 Mar

REPOSITORIES: biostudies-literature