The Ski protein negatively regulates Siah2-mediated HDAC3 degradation

Hongling Zhao, Nobuhide Ueki, Michael J. Hayman

Research output: Contribution to journalArticle

21 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)623-628
Number of pages6
JournalBiochemical and Biophysical Research Communications
Volume399
Issue number4
DOIs
StatePublished - Sep 2010
Externally publishedYes

Fingerprint

Ubiquitin-Protein Ligases
Degradation
Co-Repressor Proteins
Proteins
Association reactions
Tretinoin
Immunoprecipitation
Assays
Stabilization

Keywords

  • Co-repressor complex
  • HDAC3
  • Proteasomal degradation
  • Siah2
  • Ski

ASJC Scopus subject areas

  • Biochemistry
  • Biophysics
  • Cell Biology
  • Molecular Biology
  • Medicine(all)

Cite this

The Ski protein negatively regulates Siah2-mediated HDAC3 degradation. / Zhao, Hongling; Ueki, Nobuhide; Hayman, Michael J.

In: Biochemical and Biophysical Research Communications, Vol. 399, No. 4, 09.2010, p. 623-628.

Research output: Contribution to journalArticle

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