암세포에서의 DNA 손상 반응에 관한 CIP2A의 역할에 대한 고찰

Abstract

CIP2A (Cancerous inhibitor of PP2A) is widely known for its aberrant overexpression in various tumors and correlation with poor prognosis. Its functions related to inhibition of PP2A have been deeply investigated and MYC, AKT, and mTOR were reported to be affected by PP2A – CIP2A interaction. However, functions of CIP2A independent of PP2A are relatively unrecognized. So, we tried to elucidate the role of CIP2A in cancer irrelevant of PP2A. Here, we show that CIP2A has distinct intracellular dynamics with stress granule, and is degraded on NaAsO2, stress granule inducer. Also, we reveal that CIP2A is deeply connected with DNA repair and DNA damage response network by analyzing high-throughput gene dependency screening data. Further analysis also suggest proliferative effect of CIP2A is mainly related to ATR activity. Additional experiments show that CIP2A influences activation of ATR, possibly interacting with TOPBP1. this study identifies participation in DNA damage response as new mechanism of proliferative effect of CIP2A and provides the possibility that CIP2A might be available target for suppressing ATR as inhibition of ATR activity has been investigated for new chemotherapeutic strategy.