Regulation of the stability and transcriptional activity of NFATc4 by ubiquitination.

Abstract:

:Nuclear factor of activated T cells (NFATc4) has been implicated as a critical regulator of the cardiac development and hypertrophy. However, the mechanisms for regulating NFATc4 stability and transactivation remain unclear. We showed that NFATc4 protein was predominantly ubiquitinated through the formation of Lysine 48-linked polyubiquitin chains, and this modification decreased NFATc4 protein levels and its transcriptional activity. Furthermore, activation of GSK3beta markedly enhanced NFATc4 ubiquitination and decreased its transactivation, whereas inhibition of GSK3beta had opposite effects. Importantly, ubiquitination and phosphorylation induced by GSK3beta repressed NFATc4-dependent cardiac-specific gene expression. These results demonstrate that the ubiquitin-proteasome system plays an important role in regulating NFATc4 stability and transactivation.

journal_name

FEBS Lett

journal_title

FEBS letters

authors

Fan Y,Xie P,Zhang T,Zhang H,Gu D,She M,Li H

doi

10.1016/j.febslet.2008.11.009

subject

Has Abstract

pub_date

2008-12-10 00:00:00

pages

4008-14

issue

29

eissn

0014-5793

issn

1873-3468

pii

S0014-5793(08)00910-1

journal_volume

582

pub_type

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