PKCδ promotes etoposide-induced cell death by phosphorylating Hsp27 in HeLa cells.

Abstract:

:We investigated the regulation of Hsp27 phosphorylation by protein kinase C δ (PKCδ) during etoposide-induced apoptosis. The phosphorylation of Hsp27 at Ser78 was temporally correlated with the proteolytic activation of PKCδ during apoptosis. Hsp27 phosphorylation was dependent on the activity of PKCδ since treatment with rottlerin, a chemical inhibitor of PKCδ, or overexpression of a PKCδ dominant negative mutant abolished the phosphorylation. In addition, recombinant PKCδ phosphorylated Hsp27 at Ser78 in vitro. Moreover, caspase-3 was specifically activated following Hsp27 phosphorylation at Ser78. Pull-down assays using a phosphomimetic Hsp27 mutant revealed that binding between Hsp27 and cytochrome c was abolished by the phosphorylation. These results suggest that Hsp27 dissociates from cytochrome c following PKCδ-mediated phosphorylation at Ser78, which allows formation of the apoptosome and stimulates apoptotic progression.

authors

Choi JS,Oh JI,Na M,Lee SK,Joo SH

doi

10.1016/j.bbrc.2012.08.132

subject

Has Abstract

pub_date

2012-10-05 00:00:00

pages

590-5

issue

4

eissn

0006-291X

issn

1090-2104

pii

S0006-291X(12)01700-7

journal_volume

426

pub_type

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