Pharmacological inhibition of the SKP2/p300 signaling axis restricts castration-resistant prostate cancer.

ABSTRACT: SKP2, an F-box protein of the SCF type of the E3 ubiquitin ligase complex, plays an important function in driving tumorigenesis through the destruction of numerous tumor-suppressive proteins. Besides its critical role in cell cycle regulation, proto-oncogenic functions of SKP2 have also been shown in a cell cycle regulation-independent manner. Therefore, uncovering novel physiological upstream regulators of SKP2 signaling pathways would be essential to retard aggressive malignancies. Here, we report that elevation of SKP2 and EP300 transcriptomic expression is a hallmark of castration-resistant prostate cancer. We also found that SKP2 acetylation is likely a critical driven event in castration-resistant prostate cancer cells. Mechanistically, SKP2-acetylation is mediated by the p300 acetyl

SUBMITTER: Rezaeian AH 

PROVIDER: S-EPMC10006859 | biostudies-literature | 2023 Apr

REPOSITORIES: biostudies-literature