Caveolin-1 interacts with Derlin-1 and promotes ubiquitination and degradation of cyclooxygenase-2 via collaboration with p97 complex
| Autor: | Shu-Fen Chen, Chun-Hu Wu, Jun-Yang Liou, Yi-Chen Tsai, Yen-Ming Lee, Kabik Tam, Song-Kun Shyue |
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| Rok vydání: | 2013 |
| Předmět: |
Caveolin 1
Cell Cycle Proteins Protein degradation Ubiquitin-conjugating enzyme Endoplasmic-reticulum-associated protein degradation Biochemistry F-box protein Mice Ubiquitin Valosin Containing Protein Caveolin Animals Humans Molecular Biology Adenosine Triphosphatases biology Chemistry Endoplasmic reticulum Intracellular Signaling Peptides and Proteins Ubiquitination Membrane Proteins Proteins Cell Biology Cell biology Adaptor Proteins Vesicular Transport Protein Transport HEK293 Cells Cyclooxygenase 2 Protein Synthesis and Degradation Multiprotein Complexes Proteolysis cardiovascular system biology.protein Intercellular Signaling Peptides and Proteins |
| Zdroj: | The Journal of biological chemistry. 288(46) |
| ISSN: | 1083-351X |
| Popis: | Caveolin-1 (Cav-1) interacts with and mediates protein trafficking and various cellular functions. Derlin-1 is a candidate for the retrotranslocation channel of endoplasmic reticulum proteins. However, little is known about how Derlin-1 mediates glycosylated protein degradation. Here, we identified Cav-1 as a key player in Derlin-1- and p97-mediated cyclooxygenase 2 (COX-2) ubiquitination and degradation. Derlin-1 augmented the interaction of Cav-1 and COX-2 and mediated the degradation of COX-2 in a COX-2 C terminus-dependent manner. Suppression of Cav-1 decreased the ubiquitination of COX-2, and mutation of Asn-594 to Ala to disrupt N-glycosylation at the C terminus of COX-2 reduced the interaction of COX-2 with Cav-1 but not Derlin-1. Moreover, suppression of p97 increased the ubiquitination of COX-2 and up-regulated COX-2 but not COX-1. Cav-1 enhanced the interaction of p97 with Ufd1 and Derlin-1 and collaborated with p97 to interact with COX-2. Cav-1 may be a cofactor in the interaction of Derlin-1 and N-glycosylated COX-2 and may facilitate Derlin-1- and p97 complex-mediated COX-2 ubiquitination, retrotranslocation, and degradation. |
| Databáze: | OpenAIRE |
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