Cytoplasmic relocalization and inhibition of the cyclin-dependent kinase inhibitor p27(Kip1) by PKB/Akt-mediated phosphorylation in breast cancer. (Articolo in rivista)

Type
Label
  • Cytoplasmic relocalization and inhibition of the cyclin-dependent kinase inhibitor p27(Kip1) by PKB/Akt-mediated phosphorylation in breast cancer. (Articolo in rivista) (literal)
Anno
  • 2002-01-01T00:00:00+01:00 (literal)
Alternative label
  • Viglietto G. 1, Motti M.L. 1, Bruni P. 2, Melillo R.M. 1, D'Alessio A. 3, Califano D. 3, Vinci F. 4, Chiappetta G. 3, Tsichlis P. 5, Bellacosa A. 6-7, Fusco A. 1, Santoro M. 1 (2002)
    Cytoplasmic relocalization and inhibition of the cyclin-dependent kinase inhibitor p27(Kip1) by PKB/Akt-mediated phosphorylation in breast cancer.
    in Nature medicine (Print)
    (literal)
Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#autori
  • Viglietto G. 1, Motti M.L. 1, Bruni P. 2, Melillo R.M. 1, D'Alessio A. 3, Califano D. 3, Vinci F. 4, Chiappetta G. 3, Tsichlis P. 5, Bellacosa A. 6-7, Fusco A. 1, Santoro M. 1 (literal)
Pagina inizio
  • 1136 (literal)
Pagina fine
  • 1144 (literal)
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  • Impact Factor = 27,906; Interdisciplinariet√† del prodotto :The Authors belong to different scientific areas, sectors and Istitutions. The paper was in collaboration with International Institutions. (literal)
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  • 8 (literal)
Rivista
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  • The cyclin-dependent kinase inhibitor p27(kip1) is a putative tumor suppressor for human cancer. The mechanism underlying p27(kip1) deregulation in human cancer is, however, poorly understood. We demonstrate that the serine/threonine kinase Akt regulates cell proliferation in breast cancer cells by preventing p27(kip1)-mediated growth arrest. Threonine 157 (T157), which maps within the nuclear localization signal of p27(kip1), is a predicted Akt-phosphorylation site. Akt-induced T157 phosphorylation causes retention of p27(kip1) in the cytoplasm, precluding p27(kip1)-induced G1 arrest. Conversely, the p27(kip1)-T157A mutant accumulates in cell nuclei and Akt does not affect p27(kip1)-T157A-mediated cell cycle arrest. Lastly, T157-phosphorylated p27(kip1) accumulates in the cytoplasm of primary human breast cancer cells coincident with Akt activation. Thus, cytoplasmic relocalization of p27(kip1), secondary to Akt-mediated phosphorylation, is a novel mechanism whereby the growth inhibitory properties of p27(kip1) are functionally inactivated and the proliferation of breast cancer cells is sustained. (literal)
Note
  • ISI Web of Science (WOS) (literal)
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  • 1 Istituto di Endocrinologia ed Oncologia Sperimentale, CNR c/o Dipartimento di Biologia e Patologia Cellulare e Molecolare, Naples, Italy 2 Dipartimento di Biochimica e Biotecnologie Mediche, Naples, Italy 3 INT \"Fondazione Pascale\", Naples, Italy 4 Dip. Chimica Organica e Biochimica, Naples, Italy 5 Kimmel Cancer Center, Jefferson Medical College, Philadelphia, USA 6 Fox Chase Cancer Center, Philadelphia, USA 7 Dpt. Medical Genetics, Catholic University, Medical School, Rome, Italy (literal)
Titolo
  • Cytoplasmic relocalization and inhibition of the cyclin-dependent kinase inhibitor p27(Kip1) by PKB/Akt-mediated phosphorylation in breast cancer. (literal)
Abstract
  • The cyclin-dependent kinase inhibitor p27(kip1) is a putative tumor suppressor for human cancer. The mechanism underlying p27(kip1) deregulation in human cancer is, however, poorly understood. We demonstrate that the serine/threonine kinase Akt regulates cell proliferation in breast cancer cells by preventing p27(kip1)-mediated growth arrest. Threonine 157 (T157), which maps within the nuclear localization signal of p27(kip1), is a predicted Akt-phosphorylation site. Akt-induced T157 phosphorylation causes retention of p27(kip1) in the cytoplasm, precluding p27(kip1)-induced G1 arrest. Conversely, the p27(kip1)-T157A mutant accumulates in cell nuclei and Akt does not affect p27(kip1)-T157A-mediated cell cycle arrest. Lastly, T157-phosphorylated p27(kip1) accumulates in the cytoplasm of primary human breast cancer cells coincident with Akt activation. Thus, cytoplasmic relocalization of p27(kip1), secondary to Akt-mediated phosphorylation, is a novel mechanism whereby the growth inhibitory properties of p27(kip1) are functionally inactivated and the proliferation of breast cancer cells is sustained. (literal)
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