The antiapoptotic role of Bcl-2 can be regulated by its phosphorylation in serine and threonine residues located in a nonstructured loop that links BH3 and BH4 domains. p38 MAPK has been identified as one of the kinases able to mediate such phosphorylation, through direct interaction with Bcl-2 protein in the mitochondrial compartment. In this study, we identify, by using mass spectrometry techniques and specific anti-phosphopeptide antibodies, Ser(87) and Thr(56) as the Bcl-2 residues phosphorylated by p38 MAPK and show that phosphorylation of these residues is always associated with a decrease in the antiapoptotic potential of Bcl-2 protein. Furthermore, we obtained evidence that p38 MAPK-induced Bcl-2 phosphorylation plays a key role in the early events following serum deprivation in embryonic fibroblasts. Both cytochrome c release and caspase activation triggered by p38 MAPK activation and Bcl-2 phosphorylation are absent in embryonic fibroblasts from p38 alpha knock-out mice (p38 alpha(-/-) MEF), whereas they occur within 12 h of serum withdrawal in p38 alpha(-/-) MEF; moreover, they can be prevented by p38 MAPK inhibitors and are not associated with the synthesis of the proapoptotic proteins Bax and Fas. Thus, Bcl-2 phosphorylation by activated p38 MAPK is a key event in the early induction of apoptosis under conditions of cellular stress.
De Chiara G., M.M. (2006). Bcl-2 phosphorylation by p38 MAPK: Identification of target sites and biologic consequences. THE JOURNAL OF BIOLOGICAL CHEMISTRY, 281(30), 21353-21361.
|Tipologia:||Articolo su rivista|
|Citazione:||De Chiara G., M.M. (2006). Bcl-2 phosphorylation by p38 MAPK: Identification of target sites and biologic consequences. THE JOURNAL OF BIOLOGICAL CHEMISTRY, 281(30), 21353-21361.|
|IF:||Con Impact Factor ISI|
|Settore Scientifico Disciplinare:||Settore MED/07 - Microbiologia e Microbiologia Clinica|
|Revisione (peer review):||Sì, ma tipo non specificato|
|Digital Object Identifier (DOI):||http://dx.doi.org/10.1074/jbc.M511052200|
|Stato di pubblicazione:||Pubblicato|
|Data di pubblicazione:||2006|
|Titolo:||Bcl-2 phosphorylation by p38 MAPK: Identification of target sites and biologic consequences|
|Autori:||De Chiara G., Marcocci M.E., Torcia M., Lucibello M., Rosini P., Bonini P., Higashimoto Y., Damonte G., Armirotti A., Amodei S., Palamara A.T., Russo T., Garaci E., Cozzolino F.|
|Appare nelle tipologie:||01 - Articolo su rivista|