Journal
CELL CYCLE
Volume 12, Issue 24, Pages 3770-3780Publisher
LANDES BIOSCIENCE
DOI: 10.4161/cc.26660
Keywords
Cdc25A; CDK2; cell cycle; G(1)/S checkpoint; p53; SMG-1; tumorigenesis; tumor suppressor
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Funding
- Swedish Cancer Society
- Swedish Children's Cancer Foundation
- Swedish Research Council
- Swedish Pain Relief Foundation
- European Research Council
- Torsten and Ragnar Soderberg Foundation
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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.
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