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Your search keyword '"Rosini, Paolo"' showing total 2 results
Start Over Author "Rosini, Paolo" Topic proto-oncogene proteins c-bcl-2
2 results on '"Rosini, Paolo"'

1. Bcl-2 Phosphorylation by p38 MAPK: identification of target sites and biologic consequences.

Author

De Chiara G, Marcocci ME, Torcia M, Lucibello M, Rosini P, Bonini P, Higashimoto Y, Damonte G, Armirotti A, Amodei S, Palamara AT, Russo T, Garaci E, and Cozzolino F

Subjects
Animals, Caspases metabolism, Cytochromes c chemistry, Dogs, Enzyme Activation, Humans, MAP Kinase Signaling System, Mice, Mice, Knockout, Peptides chemistry, bcl-2-Associated X Protein metabolism, fas Receptor metabolism, Proto-Oncogene Proteins c-bcl-2 metabolism, p38 Mitogen-Activated Protein Kinases metabolism
Abstract

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 p38alpha knock-out mice (p38alpha(-/-) MEF), whereas they occur within 12 h of serum withdrawal in p38alpha(+/+) 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.

Published
2006
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2. Bcl-2 Phosphorylation by p38 MAPK: identification of target sites and biologic consequences

Author

Chiara, G., Marcocci, Me, Maria Torcia, Lucibello, M., Rosini, Paolo, Bonini, Paolo, Higashimoto, Y., Damonte, G., Armirotti, A., Amodei, S., Palamara, At, Russo, T., Garaci, E., Federico Cozzolino, De Chiara, G, Marcocci, Me, Torcia, M, Lucibello, M, Rosini, P, Bonini, P, Higashimoto, Y, Damonte, G, Armirotti, A, Amodei, S, Palamara, At, Russo, Tommaso, Garaci, E, and Cozzolino, F.

Subjects
C-JUN, MAP Kinase Signaling System, CARDIAC MYOCYTES, BCL-X(L), p38 Mitogen-Activated Protein Kinases, Mice, Dogs, FAMILY PROTEINS, Animals, Humans, POLYACRYLAMIDE-GELS, fas Receptor, INDUCED APOPTOSIS, bcl-2-Associated X Protein, Mice, Knockout, B-CELL LINE, ACTIVATED PROTEIN-KINASE, DNA-DAMAGE, DEATH, Cytochromes c, Settore MED/07 - Microbiologia e Microbiologia Clinica, Enzyme Activation, Proto-Oncogene Proteins c-bcl-2, Caspases, Peptides
Abstract

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 p38alpha knock-out mice (p38alpha(-/-) MEF), whereas they occur within 12 h of serum withdrawal in p38alpha(+/+) 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.

Published
2006

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