Data di Pubblicazione:
2001
Citazione:
Damaged microtubules can inactivate BCL-2 by means of the mTOR kinase / A. Calastretti, A. Bevilacqua, C. Ceriani, S. Viganò, P. Zancai, S. Capaccioli, A. Nicolin. - In: ONCOGENE. - ISSN 0950-9232. - 20:43(2001 Sep 27), pp. 6172-6180. [10.1038/sj.onc.1204751]
Abstract:
Rapamycin, a specific inhibitor of the serine/threonine mTOR kinase, markedly inhibited both cell growth and apoptosis in human B-cell lines. Besides arresting cells in G(1) by increasing p27(kip1), rapamycin tripled the cellular level of the BCL-2 protein. The activity was dose-dependent and specific for the p27(kip1) and BCL-2 proteins. Rapamycin did not affect bcl-2 mRNA although it increased cellular BCL-2 concentration by inhibiting phosphorylation, a mechanism initiating the decay process. To add new insight, we combined rapamycin treatment with treatment by taxol, which, by damaging microtubules, can phosphorylate BCL-2 and activate apoptosis. It was found that the mTOR kinase was activated in cells treated with taxol or with nocodazole although it was inhibited in cells pre-treated with rapamycin. BCL-2 phosphorylation, apoptosis and hyperdiploidy were also inhibited by rapamycin. In contrast, taxol-induced microtubule stabilization or metaphase synchronization were not inhibited by rapamycin. Taken together, these findings indicate that mTOR belongs to the enzymatic cascade that, starting from damaged microtubules, phosphorylates BCL-2. By regulating apoptosis, in addition to the control of a multitude of growth-related pathways, mTOR plays a nodal role in signaling G(1) and G(2)-M events.
Tipologia IRIS:
01 - Articolo su periodico
Keywords:
Apoptosis; BCL-2; Microtubules; mTOR; p27; Rapamycin
Elenco autori:
A. Calastretti, A. Bevilacqua, C. Ceriani, S. Viganò, P. Zancai, S. Capaccioli, A. Nicolin
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