SMG-1 suppresses CDK2 and tumor growth by regulating both the p53 and Cdc25A signaling pathways
2013 (English)In: Cell Cycle, ISSN 1538-4101, E-ISSN 1551-4005, Vol. 12, no 24, 3770-3780 p.Article in journal (Refereed) Published
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.
Place, publisher, year, edition, pages
2013. Vol. 12, no 24, 3770-3780 p.
Cdc25A, CDK2, cell cycle, G1/S checkpoint, p53, SMG-1, tumorigenesis, tumor suppressor
Biochemistry and Molecular Biology Cell Biology
IdentifiersURN: urn:nbn:se:su:diva-96163DOI: 10.4161/cc.26660ISI: 000330524800016OAI: oai:DiVA.org:su-96163DiVA: diva2:663648