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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
3
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pubmed:dateCreated |
2001-3-20
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pubmed:abstractText |
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.
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pubmed:commentsCorrections |
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Antigens, Neoplasm,
http://linkedlifedata.com/resource/pubmed/chemical/Cdkn1a protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Cyclin-Dependent Kinase Inhibitor...,
http://linkedlifedata.com/resource/pubmed/chemical/Cyclins,
http://linkedlifedata.com/resource/pubmed/chemical/Enzyme Inhibitors,
http://linkedlifedata.com/resource/pubmed/chemical/Protein-Serine-Threonine Kinases,
http://linkedlifedata.com/resource/pubmed/chemical/Proto-Oncogene Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Proto-Oncogene Proteins c-akt,
http://linkedlifedata.com/resource/pubmed/chemical/Receptor, erbB-2
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pubmed:status |
MEDLINE
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pubmed:month |
Mar
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pubmed:issn |
1465-7392
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:volume |
3
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
245-52
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pubmed:dateRevised |
2009-11-19
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pubmed:meshHeading |
pubmed-meshheading:11231573-3T3 Cells,
pubmed-meshheading:11231573-Adenocarcinoma,
pubmed-meshheading:11231573-Amino Acid Motifs,
pubmed-meshheading:11231573-Animals,
pubmed-meshheading:11231573-Antigens, Neoplasm,
pubmed-meshheading:11231573-Blotting, Western,
pubmed-meshheading:11231573-Breast Neoplasms,
pubmed-meshheading:11231573-Cell Division,
pubmed-meshheading:11231573-Cell Fractionation,
pubmed-meshheading:11231573-Cell Line,
pubmed-meshheading:11231573-Cyclin-Dependent Kinase Inhibitor p21,
pubmed-meshheading:11231573-Cyclins,
pubmed-meshheading:11231573-Cytoplasm,
pubmed-meshheading:11231573-Enzyme Inhibitors,
pubmed-meshheading:11231573-Female,
pubmed-meshheading:11231573-Fibroblasts,
pubmed-meshheading:11231573-Gene Expression Regulation,
pubmed-meshheading:11231573-Mice,
pubmed-meshheading:11231573-Microscopy, Fluorescence,
pubmed-meshheading:11231573-Phosphorylation,
pubmed-meshheading:11231573-Protein Transport,
pubmed-meshheading:11231573-Protein-Serine-Threonine Kinases,
pubmed-meshheading:11231573-Proto-Oncogene Proteins,
pubmed-meshheading:11231573-Proto-Oncogene Proteins c-akt,
pubmed-meshheading:11231573-Receptor, erbB-2,
pubmed-meshheading:11231573-Signal Transduction,
pubmed-meshheading:11231573-Transfection
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pubmed:year |
2001
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pubmed:articleTitle |
Cytoplasmic localization of p21Cip1/WAF1 by Akt-induced phosphorylation in HER-2/neu-overexpressing cells.
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pubmed:affiliation |
Department of Molecular and Cellular Oncology, Breast Cancer Basic Research Program, University of Texas M. D. Anderson Cancer Center, Houston, Texas 77030, USA.
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pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.,
Research Support, U.S. Gov't, Non-P.H.S.,
Research Support, Non-U.S. Gov't
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