Mdm2 is required for HDAC3 monoubiquitination and stability.

Abstract:

:HDAC3, one of the class I histone deacetylase modulates epigenetic landscape through histone modification. HDAC3 also interacts with non-histone proteins including p53 for deacetylation. Moreover, HDAC3 serves as a transcriptional repressor, interacting with NCor1/SMRT complex. Although HDAC3 plays a critical role for cellular homeostasis, regulatory mechanism of HDAC3 have been poorly understood. Here we report a novel regulatory mechanism of HDAC3 about its monoubiquitination and stabilization by Mdm2. HDAC3 levels were increased by ectopic expression of Mdm2 and decreased by Mdm2 ablation in various cell lines. We found that Mdm2 directly interacts with HDAC3 and induces HDAC3 protein levels without alteration of mRNA levels. Ectopic expression of wild type but not RING mutant of Mdm2 increased HDAC3 monoubiquitination. In addition, MdmX is beneficial for mdm2-mediated HDAC3 regulation. Ablation of Mdm2 and Mdm2/MdmX decreased cell migration along with the decrease of HDAC3 levels. These data provide an evidence that Mdm2 positively regulates HDAC3 monoubiquitination and stability.

authors

Choi YM,An S,Bae S,Jung JH

doi

10.1016/j.bbrc.2019.07.052

subject

Has Abstract

pub_date

2019-09-17 00:00:00

pages

353-358

issue

2

eissn

0006-291X

issn

1090-2104

pii

S0006-291X(19)31402-0

journal_volume

517

pub_type

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