CIP2A에 의한 PLK4 분해 조절

Abstract

The overexpression of cancerous inhibitor of protein phosphatase 2A (CIP2A), a 90kDa oncoprotein, is observed in several human cancer and correlated with cancer progression. CIP2A interacts with Protein Phosphatase 2A (PP2A) which is known as a tumor suppressor and inhibits PP2A activity to c-MYC. Therefore, CIP2A promotes cancer cell proliferation. However, the other oncogenic function of CIP2A has not been studied well. In this study, PLK4 has been discovered as a new binding partner for CIP2A. I observed CIP2A inhibits PLK4 ubiquitylation and consequently increases protein half-life by stabilizing PLK4. Therefore, overexpression of CIP2A increases PLK4 levels. PLK4 is a master regulator of centriole duplication and high PLK4 levels are a cause of centriole amplification. But, contrary to expectation, CIP2A overexpression did not lead to centriole overduplication. Thus, further study is required to uncover the effect of overexpression of PLK4 by CIP2A.