Promiscuous actions of small molecule inhibitors of the protein kinase D-class IIa HDAC axis in striated muscle.

Abstract:

:PKD-mediated phosphorylation of class IIa HDACs frees the MEF2 transcription factor to activate genes that govern muscle differentiation and growth. Studies of the regulation and function of this signaling axis have involved MC1568 and Gö-6976, which are small molecule inhibitors of class IIa HDAC and PKD catalytic activity, respectively. We describe unanticipated effects of these compounds. MC1568 failed to inhibit class IIa HDAC catalytic activity in vitro, and exerted divergent effects on skeletal muscle differentiation compared to a bona fide inhibitor of these HDACs. In cardiomyocytes, Gö-6976 triggered calcium signaling and activated stress-inducible kinases. Based on these findings, caution is warranted when employing MC1568 and Gö-6976 as pharmacological tool compounds to assess functions of class IIa HDACs and PKD.

journal_name

FEBS Lett

journal_title

FEBS letters

authors

Lemon DD,Harrison BC,Horn TR,Stratton MS,Ferguson BS,Wempe MF,McKinsey TA

doi

10.1016/j.febslet.2015.03.017

subject

Has Abstract

pub_date

2015-04-28 00:00:00

pages

1080-8

issue

10

eissn

0014-5793

issn

1873-3468

pii

S0014-5793(15)00193-3

journal_volume

589

pub_type

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