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 Lettjournal_title
FEBS lettersauthors
Lemon DD,Harrison BC,Horn TR,Stratton MS,Ferguson BS,Wempe MF,McKinsey TAdoi
10.1016/j.febslet.2015.03.017subject
Has Abstractpub_date
2015-04-28 00:00:00pages
1080-8issue
10eissn
0014-5793issn
1873-3468pii
S0014-5793(15)00193-3journal_volume
589pub_type
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