Activation of p73 upon genotoxic treatment triggers apoptosis of tumor cells lacking functional p53 and involves the activities of c-Abl and p300. Here, we demonstrate that conformational changes of p73 catalyzed by the prolyl isomerase Pin1 are crucial in this pathway. Lack of Pin1 reduces p73 stability, hampering its accumulation upon genotoxic stress. Indeed, we show that upon treatment with chemotherapeutic drugs c-Abl enhances the phosphorylation-dependent interaction between Pin1 and p73, and this in turn promotes p73 acetylation by p300. Consistently, the ability of c-Abl and p300 to increase p73 stability and transcriptional activity requires Pinl. As a consequence, Pinl appears to be essential for activation of the apoptotic response by endogenous p73.

Pin1 links the activities of c-Abl and p300 in regulating p73 function / F. Mantovani, S. Piazza, M. Gostissa, S. Strano, P. Zacchi, R. Mantovani, G. Blandino, G. Del Sal. - In: MOLECULAR CELL. - ISSN 1097-2765. - 14:5(2004 Jun 04), pp. 625-636.

Pin1 links the activities of c-Abl and p300 in regulating p73 function

R. Mantovani;
2004

Abstract

Activation of p73 upon genotoxic treatment triggers apoptosis of tumor cells lacking functional p53 and involves the activities of c-Abl and p300. Here, we demonstrate that conformational changes of p73 catalyzed by the prolyl isomerase Pin1 are crucial in this pathway. Lack of Pin1 reduces p73 stability, hampering its accumulation upon genotoxic stress. Indeed, we show that upon treatment with chemotherapeutic drugs c-Abl enhances the phosphorylation-dependent interaction between Pin1 and p73, and this in turn promotes p73 acetylation by p300. Consistently, the ability of c-Abl and p300 to increase p73 stability and transcriptional activity requires Pinl. As a consequence, Pinl appears to be essential for activation of the apoptotic response by endogenous p73.
prolyl isomerase pin1 ; dna-damage ; cell-cycle ; p53-dependent apoptosis ; p53-related protein ; induce apoptosis ; family-members ; breast-cancer ; target genes ; p53
Settore BIO/18 - Genetica
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2434/65165
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