SMG-1 suppresses CDK2 and tumor growth by regulating both the p53 and Cdc25A signaling pathways.

Gubanova E, Issaeva N, Gokturk C, Djureinovic T, Helleday T

Cell Cycle 12 (24) 3770-3780 [2013-12-15; online 2013-10-04]

The DNA damage response is coordinated by phosphatidylinositol 3-kinase-related kinases, ATM, ATR, and DNA-PK. SMG-1 is the least studied stress-responsive member of this family. Here, we show that SMG-1 regulates the G 1/S checkpoint through both a p53-dependent, and a p53-independent pathway. We identify Cdc25A as a new SMG-1 substrate, and show that cells depleted of SMG-1 exhibit prolonged Cdc25A stability, failing to inactivate CDK2 in response to radiation. Given an increased tumor growth following depletion of SMG-1, our data demonstrate a novel role for SMG-1 in regulating Cdc25A and suppressing oncogenic CDK2 driven proliferation, confirming SMG-1 as a tumor suppressor.

Affiliated researcher

PubMed 24107632

DOI 10.4161/cc.26660

Crossref 10.4161/cc.26660

pii: 26660
pmc: PMC3905069


Publications 7.1.2