Bcl-2 phosphorylation and apoptosis activated by damaged microtubules require mTOR and are regulated by Akt (Articolo in rivista)

Type
Label
  • Bcl-2 phosphorylation and apoptosis activated by damaged microtubules require mTOR and are regulated by Akt (Articolo in rivista) (literal)
Anno
  • 2004-01-01T00:00:00+01:00 (literal)
Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#doi
  • 10.1038/sj.onc.1207698 (literal)
Alternative label
  • Laura Asnaghi1; Angela Calastretti1; Annamaria Bevilacqua1; Igea D'Agnano2; Giuliana Gatti1; Gianfranco Canti1; Domenico Delia3; Sergio Capaccioli4; Angelo Nicolin1 (2004)
    Bcl-2 phosphorylation and apoptosis activated by damaged microtubules require mTOR and are regulated by Akt
    in Oncogene (Basingstoke)
    (literal)
Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#autori
  • Laura Asnaghi1; Angela Calastretti1; Annamaria Bevilacqua1; Igea D'Agnano2; Giuliana Gatti1; Gianfranco Canti1; Domenico Delia3; Sergio Capaccioli4; Angelo Nicolin1 (literal)
Pagina inizio
  • 5781 (literal)
Pagina fine
  • 5791 (literal)
Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#numeroVolume
  • 23 (literal)
Rivista
Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#pagineTotali
  • 11 (literal)
Note
  • PubMe (literal)
Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#affiliazioni
  • 1Department of Pharmacology, University of Milan, Via Vanvitelli 32, 20129 Milan, Italy; 2Institute of Biochemical Technologies-CNR, 20090 Milan, Italy; 3Department of Experimental Oncology, Istituto Nazionale Tumori, 20133 Milan, Italy; 4Institute of General Pathology, University of Florence, 50134 Florence, Italy (literal)
Titolo
  • Bcl-2 phosphorylation and apoptosis activated by damaged microtubules require mTOR and are regulated by Akt (literal)
Abstract
  • The serine/threonine kinase mTOR, the major sensor of cell growth along the PI3K/Akt pathway, can be activated by agents acting on microtubules. Damaged microtubules induce phosphorylation ofthe Bcl-2 protein and lower the threshold ofprogra mmed cell death, both ofwhich are inhibited by rapamycin. In HEK293 cells expressing Akt mutants, the level ofBcl-2 phosphorylation and the threshold ofapopto sis induced by taxol or by nocodazole are significantly modified. In cells expressing dominantnegative Akt (DN-Akt), Bcl-2 phosphorylation and p70S6KThr421/Ser424 phosphorylation induced by taxol or nocodazole were significantly enhanced as compared to cells expressing constitutively active Akt (CA-Akt) and inhibited by rapamycin. Moreover, DN-Akt cells were more sensitive to antitubule agents than CA-Akt cells. In nocodazole-treated HEK293 cells sorted according to cell cycle, the p70S6KThr421/Ser424 phosphorylation was associated to the G2/M fraction. More relevant, nocodazole inhibited, in a dose-response manner, mTOR phosphorylation at Ser2448. This activity, potentiated in DN-Akt cells, was not detectable in CA-Akt cells. Our results suggest that death signals originating from damaged microtubules in G2/M can compete with G1 survival pathways at the level ofmTOR . These findings have implications for cancer therapy and drug resistance. (literal)
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