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- Title
Cytoplasmic localization of p21<sup>Cip1/WAF1</sup> by Akt-induced phosphorylation in HER-2/neu-overexpressing cells.
- Authors
Zhou, Binhua P.; Liao, Yong; Xia, Weiya; Spohn, Bill; Lee, Mong-Hong; Hung, Mien-Chie
- Abstract
Amplification or overexpression of HER-2/neu in cancer cells confers resistance to apoptosis and promotes cell growth. The cellular localization of p21[SUPCip1/WAF1] has been proposed to be critical either in promoting cell survival or in inhibiting cell growth. Here we show that HER-2/neu-mediated cell growth requires the activation of Akt, which associates with p21[SUPCip1/WAF1] and phosphorylates it at threonine 145, resulting in cytoplasmic localization of p21[SUPCip1/WAF1]. Furthermore, blocking the Akt pathway with a dominant-negative Akt mutant restores the nuclear localization and cell-growth-inhibiting activity of p21[SUPCip1/WAF1]. Our results indicate that HER-2/neu induces cytoplasmic localization of p21[SUPCip1/WAF1] through activation of Akt to promote cell growth, which may have implications for the oncogenic activity of HER-2/neu and Akt.
- Subjects
CELL proliferation; CANCER cells
- Publication
Nature Cell Biology, 2001, Vol 3, Issue 3, p245
- ISSN
1465-7392
- Publication type
Article
- DOI
10.1038/35060032