Regulation of Endoplasmic Reticulum-associated Degradation by RNF5-dependent Ubiquitination of JNK-associated Membrane Protein (JAMP)
| Autor: | Takayuki Kadoya, Marianna Tcherpakov, Julia I. Toth, Ze'ev Ronai, Agnes Delaunay, Matthew D. Petroski |
|---|---|
| Rok vydání: | 2009 |
| Předmět: |
Proteasome Endopeptidase Complex
Protein Folding Receptors Antigen T-Cell alpha-beta Ubiquitin-Protein Ligases Cystic Fibrosis Transmembrane Conductance Regulator Biology Endoplasmic-reticulum-associated protein degradation Ubiquitin-conjugating enzyme Endoplasmic Reticulum Biochemistry JUNQ and IPOD Stress Physiological Humans Molecular Biology Membrane Glycoproteins Protein Synthesis Post-Translational Modification and Degradation Endoplasmic reticulum Ubiquitination Membrane Proteins Cell Biology Cell biology Ubiquitin ligase DNA-Binding Proteins Proteasome Membrane protein Proteasome assembly Ubiquitin-Conjugating Enzymes biology.protein Carrier Proteins HeLa Cells |
| Zdroj: | Journal of Biological Chemistry. 284:12099-12109 |
| ISSN: | 0021-9258 |
| DOI: | 10.1074/jbc.m808222200 |
| Popis: | Clearance of misfolded proteins by endoplasmic reticulum (ER)-associated degradation (ERAD) requires concerted activity of chaperones, adaptor proteins, ubiquitin ligases, and proteasomes. RNF5 is a ubiquitin ligase anchored to the ER membrane implicated in ERAD via ubiquitination of misfolded proteins. Among RNF5-associated proteins is JNK-associated membrane protein (JAMP), a 7-transmembrane protein located within the ER membrane that facilitates degradation of misfolded proteins through recruitment of proteasomes and ERAD regulatory components. Here we demonstrate that RNF5 associates with JAMP in the ER membrane. This association results in Ubc13-dependent RNF5-mediated noncanonical ubiquitination of JAMP. This ubiquitination does not alter JAMP stability but rather inhibits its association with Rpt5 and p97. Consequently, clearance of misfolded proteins, such as CFTRΔ508 and T cell receptor α, is less efficient, resulting in their greater accumulation. Significantly, the RNF5 effect on JAMP is seen prior to and after ER stress response, thereby highlighting a novel mechanism to limit ERAD and proteasome assembly at the ER, to the actual ER stress response. |
| Databáze: | OpenAIRE |
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