SMG-1 Suppresses CDK2 and Tumor Growth by Regulating Both the P53 and Cdc25A Signaling Pathways

Overview

Journal Cell Cycle

Specialty Cell Biology

Date 2013 Oct 11

PMID 24107632

Citations 23

Authors

Evgenia Gubanova

Natalia Issaeva

Camilla Gokturk

Tatjana Djureinovic

Thomas Helleday

Affiliations

Soon will be listed here.

Abstract

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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