Cytoplasmic localization of p21 CIP1/WAF1 by Akt-induced phosphorylation in HER-2/neu-overexpressing cells

B. P. Zhou; Y. Liao; W. Xia; B. Spohn; M. H. Lee; M. C. Hung

doi:10.1038/35060032

Cytoplasmic localization of p21 ^CIP1/WAF1 by Akt-induced phosphorylation in HER-2/neu-overexpressing cells

B. P. Zhou, Y. Liao, W. Xia, B. Spohn, M. H. Lee, M. C. Hung

Research output: Contribution to journal › Article › peer-review

933 Scopus citations

Abstract

Amplification or overexpression of HER-2/neu in cancer cells confers resistance to apoptosis and promotes cell growth. The cellular localization of p21^Cip1/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^Cip1/WAF1 and phosphorylates it at threonine 145, resulting in cytoplasmic localization of p21^Cip1/WAF1. Furthermore, blocking the Akt pathway with a dominant-negative Akt mutant restores the nuclear localization and cell-growth-inhibiting activity of p21^Cip1/WAF1. Our results indicate that HER-2/neu induces cytoplasmic localization of p21^Cip1/WAF1 through activation of Akt to promote cell growth, which may have implications for the oncogenic activity of HER-2/neu and Akt.

Original language	English
Pages (from-to)	245-252
Number of pages	8
Journal	Nature Cell Biology
Volume	3
Issue number	3
DOIs	https://doi.org/10.1038/35060032
State	Published - 2001

Bibliographical note

Funding Information:
ACKNOWLEDGEMENTS We thank D. Yu, R. B. Arlinghaus and W. H. Klein for critical comments on the manuscript. This work was supported by grants from the National Institutes of Health (to M-C.H.), by a SPORE grant in ovarian cancer (to M-C.H.), and by the Nellie Connally Breast Cancer Research Fund at the M. D. Anderson Cancer Center (M-C.H.). B.P.Z. is a recipient of a postdoctoral fellowship from the US Department of Defense Breast Cancer Research. Correspondence and requests for materials should be addressed to M-C.H.

ASJC Scopus subject areas

Cell Biology

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

Access to Document

10.1038/35060032

Cite this

@article{37f45bfeddc541e393a4218c012904dd,

title = "Cytoplasmic localization of p21 CIP1/WAF1 by Akt-induced phosphorylation in HER-2/neu-overexpressing cells",

abstract = "Amplification or overexpression of HER-2/neu in cancer cells confers resistance to apoptosis and promotes cell growth. The cellular localization of p21Cip1/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 p21Cip1/WAF1 and phosphorylates it at threonine 145, resulting in cytoplasmic localization of p21Cip1/WAF1. Furthermore, blocking the Akt pathway with a dominant-negative Akt mutant restores the nuclear localization and cell-growth-inhibiting activity of p21Cip1/WAF1. Our results indicate that HER-2/neu induces cytoplasmic localization of p21Cip1/WAF1 through activation of Akt to promote cell growth, which may have implications for the oncogenic activity of HER-2/neu and Akt.",

author = "Zhou, {B. P.} and Y. Liao and W. Xia and B. Spohn and Lee, {M. H.} and Hung, {M. C.}",

note = "Funding Information: ACKNOWLEDGEMENTS We thank D. Yu, R. B. Arlinghaus and W. H. Klein for critical comments on the manuscript. This work was supported by grants from the National Institutes of Health (to M-C.H.), by a SPORE grant in ovarian cancer (to M-C.H.), and by the Nellie Connally Breast Cancer Research Fund at the M. D. Anderson Cancer Center (M-C.H.). B.P.Z. is a recipient of a postdoctoral fellowship from the US Department of Defense Breast Cancer Research. Correspondence and requests for materials should be addressed to M-C.H.",

year = "2001",

doi = "10.1038/35060032",

language = "English",

volume = "3",

pages = "245--252",

number = "3",

}

TY - JOUR

T1 - Cytoplasmic localization of p21 CIP1/WAF1 by Akt-induced phosphorylation in HER-2/neu-overexpressing cells

AU - Zhou, B. P.

AU - Liao, Y.

AU - Xia, W.

AU - Spohn, B.

AU - Lee, M. H.

AU - Hung, M. C.

N1 - Funding Information: ACKNOWLEDGEMENTS We thank D. Yu, R. B. Arlinghaus and W. H. Klein for critical comments on the manuscript. This work was supported by grants from the National Institutes of Health (to M-C.H.), by a SPORE grant in ovarian cancer (to M-C.H.), and by the Nellie Connally Breast Cancer Research Fund at the M. D. Anderson Cancer Center (M-C.H.). B.P.Z. is a recipient of a postdoctoral fellowship from the US Department of Defense Breast Cancer Research. Correspondence and requests for materials should be addressed to M-C.H.

PY - 2001

Y1 - 2001

N2 - Amplification or overexpression of HER-2/neu in cancer cells confers resistance to apoptosis and promotes cell growth. The cellular localization of p21Cip1/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 p21Cip1/WAF1 and phosphorylates it at threonine 145, resulting in cytoplasmic localization of p21Cip1/WAF1. Furthermore, blocking the Akt pathway with a dominant-negative Akt mutant restores the nuclear localization and cell-growth-inhibiting activity of p21Cip1/WAF1. Our results indicate that HER-2/neu induces cytoplasmic localization of p21Cip1/WAF1 through activation of Akt to promote cell growth, which may have implications for the oncogenic activity of HER-2/neu and Akt.

AB - Amplification or overexpression of HER-2/neu in cancer cells confers resistance to apoptosis and promotes cell growth. The cellular localization of p21Cip1/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 p21Cip1/WAF1 and phosphorylates it at threonine 145, resulting in cytoplasmic localization of p21Cip1/WAF1. Furthermore, blocking the Akt pathway with a dominant-negative Akt mutant restores the nuclear localization and cell-growth-inhibiting activity of p21Cip1/WAF1. Our results indicate that HER-2/neu induces cytoplasmic localization of p21Cip1/WAF1 through activation of Akt to promote cell growth, which may have implications for the oncogenic activity of HER-2/neu and Akt.

UR - http://www.scopus.com/inward/record.url?scp=0034745353&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0034745353&partnerID=8YFLogxK

U2 - 10.1038/35060032

DO - 10.1038/35060032

M3 - Article

C2 - 11231573

AN - SCOPUS:0034745353

SN - 1465-7392

VL - 3

SP - 245

EP - 252

JO - Nature Cell Biology

JF - Nature Cell Biology

IS - 3

ER -