Myocardial regulation of p300 and p53 by doxorubicin involves ubiquitin pathways

Circulation Journal : Official Journal of the Japanese Circulation Society
Tatsuya MorimotoKoji Hasegawa

Abstract

Doxorubicin (Dox) depletes p300 from cardiac myocytes and induces apoptosis of these cells. p300 protein possesses ubiquitin ligase activity for the p53 tumor suppressor gene product, catalyzes p53 polyubiqutination, and facilitates p53 degradation in an ubiquitin-dependent manner. The present study investigated the ubiquitin-dependent regulation of p53 by Dox and p300 in cardiac myocytes. Primary cardiac myocytes from neonatal rats were exposed to a proteasome inhibitor, MG132, in culture. MG132 increased both p300 and p53 protein levels in these cells, suggesting that ubiquitin-dependent degradation is involved in the homeostasis of these proteins. Notably, treatment of cardiac myocytes with Dox decreased the protein levels of p300 but markedly increased those of p53. By immunoprecipitation-Western blotting, it was shown that treatment with Dox decreased poly-ubiquitinated p53 but increased that of p300 in cardiac myocytes. Finally, the overexpression of p300 in cardiomyocytes suppressed the Dox-mediated increase in the p53 level in addition to inhibiting Dox-induced apoptosis. Dox reciprocally regulates p300 and p53 through ubiquitin-dependent pathways and that p300, by its ubiquitin ligase activity, is partially involved in...Continue Reading

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Citations

Jun 13, 2009·Circulation Journal : Official Journal of the Japanese Circulation Society·Tomohide TakayaKoji Hasegawa
Dec 8, 2009·Circulation Journal : Official Journal of the Japanese Circulation Society·Yoshinori YoshidaKoji Hasegawa
Mar 2, 2010·Circulation Journal : Official Journal of the Japanese Circulation Society·Tomohide TakayaKoji Hasegawa
May 15, 2010·Circulation Journal : Official Journal of the Japanese Circulation Society·Tatsuya MorimotoKoji Hasegawa
Aug 19, 2010·Circulation Journal : Official Journal of the Japanese Circulation Society·Manabu MinamiHisanori Horiuchi
Aug 23, 2011·The International Journal of Biochemistry & Cell Biology·Yung-Lung ChangShih-Ming Huang
Mar 8, 2012·Annals of Plastic Surgery·Mohammad M Al-Qattan

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