The Ski protein negatively regulates Siah2-mediated HDAC3 degradation
| Autor: | Michael J. Hayman, Nobuhide Ueki, Hong Ling Zhao |
|---|---|
| Rok vydání: | 2010 |
| Předmět: |
Proteasome Endopeptidase Complex
animal structures Leupeptins Immunoprecipitation Ubiquitin-Protein Ligases Biophysics Retinoic acid SIAH2 Cysteine Proteinase Inhibitors Biochemistry DNA-binding protein Article Histone Deacetylases chemistry.chemical_compound Proto-Oncogene Proteins Chlorocebus aethiops Enzyme Stability Animals Humans Nuclear protein Molecular Biology Psychological repression biology SKI protein Nuclear Proteins Cell Biology musculoskeletal system Ubiquitin ligase Cell biology DNA-Binding Proteins chemistry COS Cells biology.protein Proteasome Inhibitors human activities |
| Zdroj: | Biochemical and Biophysical Research Communications. 399:623-628 |
| ISSN: | 0006-291X |
| DOI: | 10.1016/j.bbrc.2010.07.127 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Full Text from ScienceDirect