Auto-acetylation stabilizes p300 in cardiac myocytes during acute oxidative stress, promoting STAT3 accumulation and cell survival.

Breast Cancer Research and Treatment
Sumit JainNanette H Bishopric

Abstract

The nuclear acetyltransferase p300 is rapidly and stably induced in the heart during hemodynamic stress, but the mechanism of this induction is unknown. To determine the role of oxidative stress in p300 induction, we exposed neonatal rat cardiac myocytes to doxorubicin (DOX, 1 μM) or its vehicle, and monitored p300 protein content and stability for 24 h. Levels of p300 rose substantially within 1 h and remained elevated for at least 24 h, while p300 transcript levels declined. In the presence of cycloheximide, the estimated half-life of p300 in control cells was approximately 4.5 h, typical of an immediate-early response protein. DOX treatment prolonged p300 t(1/2) to >24 h, indicating that the sharp rise in p300 levels was attributable to rapid protein stabilization. p300 stabilization was entirely due to an increase in acetylated p300 species with greatly enhanced resistance to proteasomal degradation. The half-life of p300 was dependent on its acetyltransferase activity, falling in the presence of p300 inhibitors curcumin and anacardic acid, and increasing with histone deacetylase (HDAC) inhibition. At the same time, acetyl-STAT3, phospho-STAT3-(Tyr 705) and -(Ser 727) increased, together with a prolongation of STAT3 half-li...Continue Reading

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Citations

Mar 30, 2013·Canadian Journal of Physiology and Pharmacology·Biao FengSubrata Chakrabarti
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Apr 17, 2021·Experimental & Molecular Medicine·Joo-Young ImMisun Won
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Aug 8, 2021·Redox Biology·Daisong LiXianming Chu
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Apr 16, 2014·Genome Research·Haloom RafehiAssam El-Osta

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