GADD34 induces p21 expression and cellular senescence.

We previously identified GADD34 (growth arrest and DNA damage protein 34) by screening for genes involved in oncogenic-transformation and/or cellular senescence in Ras-transformed rat F2408 fibroblasts (7EJ-Ras), which exhibit anchorage-independent growth and do not senesce. In the current study, we found that transduction of 7EJ-Ras cells with a retroviral vector expressing GADD34 suppressed their proliferation. Furthermore, we observed that fibroblasts derived from GADD34-knockout mice (GADD34-KO MEFs) did not undergo senescence. Whereas the expression of p21 was decreased in GADD34 KO MEFs, its expression was rescued in these cells by ectopic expression of GADD34 by retroviral transduction. These findings suggest that GADD34 contributes to the regulation of p21 expression, and that it suppresses cellular proliferation through the induction of cellular senescence.

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