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At the very least, class I HDAC inhibitors like butyrate and TSA should
at least prevent HDAC/PP1-driven deactivation of CREB if not activating
CREB outright.
Biochem Biophys Res Commun. 2009 Jan 30;379(1):1-5. Epub 2008 Dec 12.
Inactivation of CREB mediated gene transcription by HDAC8 bound protein
phosphatase.
Gao J, Siddoway B, Huang Q, Xia H.
Neuroscience Center, LSU Health Science Center, 2020 Gravier Street,
Suite D, New Orleans, LA 70112, USA.
CREB activation via phosphorylation at serine 133 and resulting CREB
mediated gene expression is a critical event which can have a
significant effect on many cellular processes, including cell survival
and plasticity. CREB can be activated by many kinases, for example, it
can be phosphorylated by PKA, MAPK, and CaMKIV. The various signaling
pathways leading to CREB activation have been extensively studied. On
the other hand, CREB is inactivated by PP1 through dephosphorylation at
S133 and not much attention has been paid to this aspect of the
signaling pathway. It was shown recently that PP1 can be targeted to
CREB, for efficient dephosphorylation, through PP1 binding protein
HDAC1. In this study, we found that another class-I HDAC family protein,
HDAC8, localized in the nucleus of HEK293 cells and also bound to both
CREB and PP1. Expression of recombinant HDAC8 results in decreased CREB
activation and CREB mediated gene transcription in response to forskolin
application. Our study thus elucidated that more than one class-I HDAC
family members can regulate the duration of CREB mediated gene
transcription.
Publication Types:
* Research Support, N.I.H., Extramural
* Research Support, Non-U.S. Gov't
PMID: 19070599 |
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