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

• 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.

Ämnesord

NATURVETENSKAP  -- Kemi -- Biokemi (hsv//swe)

NATURAL SCIENCES  -- Chemical Sciences -- Biochemistry (hsv//eng)

NATURVETENSKAP  -- Biologi -- Molekylärbiologi (hsv//swe)

NATURAL SCIENCES  -- Biological Sciences -- Molecular Biology (hsv//eng)

NATURVETENSKAP  -- Biologi -- Cellbiologi (hsv//swe)

NATURAL SCIENCES  -- Biological Sciences -- Cell Biology (hsv//eng)

MEDICIN OCH HÄLSOVETENSKAP  -- Klinisk medicin -- Cancer och onkologi (hsv//swe)

MEDICAL AND HEALTH SCIENCES  -- Clinical Medicine -- Cancer and Oncology (hsv//eng)

MEDICIN OCH HÄLSOVETENSKAP  -- Medicinska och farmaceutiska grundvetenskaper -- Cell- och molekylärbiologi (hsv//swe)

MEDICAL AND HEALTH SCIENCES  -- Basic Medicine -- Cell and Molecular Biology (hsv//eng)

NATURVETENSKAP  -- Biologi -- Utvecklingsbiologi (hsv//swe)

NATURAL SCIENCES  -- Biological Sciences -- Developmental Biology (hsv//eng)

Nyckelord

Cdc25A

CDK2

cell cycle

G1/S checkpoint

p53

SMG-1

tumorigenesis

tumor suppressor

Publikations- och innehållstyp

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