Document Detail

The Ski protein negatively regulates Siah2-mediated HDAC3 degradation.
MedLine Citation:
PMID:  20691163     Owner:  NLM     Status:  MEDLINE    
Ski acts as a transcriptional co-repressor by multiple direct and indirect interactions with several distinct repression complexes. Ski represses retinoic acid (RA) signaling by interacting with, and stabilizing, key components of the co-repressor complex, namely, HDAC3. However, little is known as to how the Ski protein can stabilize HDAC3. In the present study, we identified the Siah2 protein as a potential E3 ubiquitin ligase that mediated proteasomal degradation of HDAC3. Reciprocal co-immunoprecipitation assays further revealed that Ski interacts with Siah2. Furthermore, co-expression of the Ski protein stabilized the level of Siah2 protein. Since Siah2 regulates its own level of expression by self-degradation, the stabilization of Siah2 by Ski is an indication that Ski association leads to inhibition of Siah2 E3 ubiquitin ligase activity. Only wild-type Ski and Ski truncation mutants that were in the same complex with Siah2 could stabilize HDAC3 levels. Taken together, the results suggest that association with Ski leads to inhibition of Siah2 E3 ubiquitin ligase activity and in this way, the Ski protein inhibits Siah2-mediated proteasomal degradation of HDAC3.
Hong-Ling Zhao; Nobuhide Ueki; Michael J Hayman
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2010-08-04
Journal Detail:
Title:  Biochemical and biophysical research communications     Volume:  399     ISSN:  1090-2104     ISO Abbreviation:  Biochem. Biophys. Res. Commun.     Publication Date:  2010 Sep 
Date Detail:
Created Date:  2010-09-06     Completed Date:  2010-10-07     Revised Date:  2014-09-11    
Medline Journal Info:
Nlm Unique ID:  0372516     Medline TA:  Biochem Biophys Res Commun     Country:  United States    
Other Details:
Languages:  eng     Pagination:  623-8     Citation Subset:  IM    
Copyright Information:
Copyright 2010 Elsevier Inc. All rights reserved.
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MeSH Terms
COS Cells
Cercopithecus aethiops
Cysteine Proteinase Inhibitors / pharmacology
DNA-Binding Proteins / genetics,  metabolism*
Enzyme Stability
Histone Deacetylases / metabolism*
Leupeptins / pharmacology
Nuclear Proteins / antagonists & inhibitors,  metabolism*
Proteasome Endopeptidase Complex / metabolism*
Proteasome Inhibitors
Proto-Oncogene Proteins / genetics,  metabolism*
Ubiquitin-Protein Ligases / antagonists & inhibitors,  metabolism*
Grant Support
CA42573/CA/NCI NIH HHS; R01 CA042573/CA/NCI NIH HHS; R01 CA042573-20/CA/NCI NIH HHS; T32-CA009176/CA/NCI NIH HHS
Reg. No./Substance:
0/Cysteine Proteinase Inhibitors; 0/DNA-Binding Proteins; 0/Leupeptins; 0/Nuclear Proteins; 0/Proteasome Inhibitors; 0/Proto-Oncogene Proteins; 126648-96-2/SKI protein, human; 133407-82-6/benzyloxycarbonylleucyl-leucyl-leucine aldehyde; EC Endopeptidase Complex; EC Deacetylases; EC deacetylase 3; EC Ligases; EC in absentia proteins

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