The antiapoptotic role of Bcl-2 can be regulated by its phos- phorylation in serine and threonine residues located in a non- structured 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-phos- phopeptide antibodies, Ser87 and Thr56 as the Bcl-2 residues phosphorylated by p38 MAPK and show that phosphorylation of these residues is always associated with a decrease in the antiapo- ptotic potential of Bcl-2 protein. Furthermore, we obtained evi- dence 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 trig- gered by p38 MAPK activation and Bcl-2 phosphorylation are absent in embryonic fibroblasts from p38- knock-out mice, whereas they occur within 12 h of serum with- drawal in p38--/- 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 apopto- sis under conditions of cellular stress.

Bcl-2 phosphorylation by p38 MAPK: Identification of target sites and biologic consequences / G., De Chiara; Marcocci, Maria Elena; M., Torcia; Lucibello, MARIA TERESA; P., Rosini; P., Bovini; Y., Higascimoto; G., Da Monte; A., Armirotti; S., Amodei; Palamara, ANNA TERESA; T., Russo; E., Garaci; F., Cozzolino. - In: THE JOURNAL OF BIOLOGICAL CHEMISTRY. - ISSN 0021-9258. - 281(30):(2006), pp. 21353-21361. [10.1074/jbc.M511052200]

Bcl-2 phosphorylation by p38 MAPK: Identification of target sites and biologic consequences.

MARCOCCI, Maria Elena;LUCIBELLO, MARIA TERESA;PALAMARA, ANNA TERESA;
2006

Abstract

The antiapoptotic role of Bcl-2 can be regulated by its phos- phorylation in serine and threonine residues located in a non- structured 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-phos- phopeptide antibodies, Ser87 and Thr56 as the Bcl-2 residues phosphorylated by p38 MAPK and show that phosphorylation of these residues is always associated with a decrease in the antiapo- ptotic potential of Bcl-2 protein. Furthermore, we obtained evi- dence 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 trig- gered by p38 MAPK activation and Bcl-2 phosphorylation are absent in embryonic fibroblasts from p38- knock-out mice, whereas they occur within 12 h of serum with- drawal in p38--/- 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 apopto- sis under conditions of cellular stress.
2006
01 Pubblicazione su rivista::01a Articolo in rivista
Bcl-2 phosphorylation by p38 MAPK: Identification of target sites and biologic consequences / G., De Chiara; Marcocci, Maria Elena; M., Torcia; Lucibello, MARIA TERESA; P., Rosini; P., Bovini; Y., Higascimoto; G., Da Monte; A., Armirotti; S., Amodei; Palamara, ANNA TERESA; T., Russo; E., Garaci; F., Cozzolino. - In: THE JOURNAL OF BIOLOGICAL CHEMISTRY. - ISSN 0021-9258. - 281(30):(2006), pp. 21353-21361. [10.1074/jbc.M511052200]
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11573/365770
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