The COP9 signalosome controls ubiquitinylation of ABCA1
| Autor: | Kazumitsu Ueda, Yuya Azuma, Mie Takada, Noriyuki Kioka, Minami Maeda |
|---|---|
| Rok vydání: | 2009 |
| Předmět: |
Proteasome Endopeptidase Complex
Biophysics Biochemistry Cell Line chemistry.chemical_compound Ubiquitin MG132 polycyclic compounds Humans COP9 signalosome Molecular Biology biology COP9 Signalosome Complex Ubiquitination nutritional and metabolic diseases hemic and immune systems Cell Biology Atherosclerosis Protein ubiquitination Cholesterol chemistry Proteasome ABCA1 Multiprotein Complexes biology.protein Macrophages Peritoneal lipids (amino acids peptides and proteins) ATP-Binding Cassette Transporters Deubiquitination ATP Binding Cassette Transporter 1 Peptide Hydrolases |
| Zdroj: | Biochemical and biophysical research communications. 382(1) |
| ISSN: | 1090-2104 |
| Popis: | ATP-binding cassette protein A1 (ABCA1) mediates the transfer of cellular free cholesterol and phospholipids to apolipoprotein A-I (apoA-I), an extracellular acceptor in plasma, to form high-density lipoprotein (HDL). ABCA1 has been suggested to be degraded by proteasome in cholesterol-loaded macrophages, however, the mechanism and regulation of proteasomal degradation of ABCA1 remain unclear. In this study, we analyzed the putative interaction between ABCA1 and COP9 signalosome (CSN), a key molecule in controlling protein ubiquitination and deubiquitination. CSN2 and CSN5, subunits of COP9 CSN complex, were coprecipitated with ABCA1 when coexpressed in HEK293 cells and proteasomal degradation was inhibited by MG132. Overexpression of CSN2 increased endogenous CSN7 and CSN8, and decreased ubiquitinylated forms of ABCA1. These results suggest that CSN is a key molecule which controls the ubiquitinylation and deubiquitinylation of ABCA1, and is thus an important target for developing potential drugs to prevent atherosclerosis. |
| Databáze: | OpenAIRE |
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