RNF170 protein, an endoplasmic reticulum membrane ubiquitin ligase, mediates inositol 1,4,5-trisphosphate receptor ubiquitination and degradation
| Autor: | Justine P. Lu, Richard J.H. Wojcikiewicz, Margaret M.P. Pearce, Yuan Wang, Danielle A. Sliter |
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| Rok vydání: | 2011 |
| Předmět: |
inorganic chemicals
Proteasome Endopeptidase Complex Ubiquitin-Protein Ligases Nerve Tissue Proteins Immune receptor Endoplasmic-reticulum-associated protein degradation Biology Ubiquitin-conjugating enzyme Endoplasmic Reticulum Biochemistry Protein Structure Secondary Animals Humans Inositol 1 4 5-Trisphosphate Receptors Molecular Biology G protein-coupled receptor Endoplasmic reticulum membrane Ubiquitination Membrane Proteins STIM1 Cell Biology Inositol trisphosphate receptor Cell biology Ubiquitin ligase Rats carbohydrates (lipids) Protein Synthesis and Degradation Multiprotein Complexes Mutation biology.protein HeLa Cells Protein Binding |
| Zdroj: | The Journal of biological chemistry. 286(27) |
| ISSN: | 1083-351X |
| Popis: | Inositol 1,4,5-trisphosphate (IP(3)) receptors are endoplasmic reticulum membrane calcium channels that, upon activation, are degraded via the ubiquitin-proteasome pathway. While searching for novel mediators of IP(3) receptor processing, we discovered that RNF170, an uncharacterized RING domain-containing protein, associates rapidly with activated IP(3) receptors. RNF170 is predicted to have three membrane-spanning helices, is localized to the ER membrane, and possesses ubiquitin ligase activity. Depletion of endogenous RNF170 by RNA interference inhibited stimulus-induced IP(3) receptor ubiquitination, and degradation and overexpression of a catalytically inactive RNF170 mutant suppressed stimulus-induced IP(3) receptor processing. A substantial proportion of RNF170 is constitutively associated with the erlin1/2 (SPFH1/2) complex, which has been shown previously to bind to IP(3) receptors immediately after their activation. Depletion of RNF170 did not affect the binding of the erlin1/2 complex to stimulated IP(3) receptors, whereas erlin1/2 complex depletion inhibited RNF170 binding. These results suggest a model in which the erlin1/2 complex recruits RNF170 to activated IP(3) receptors where it mediates IP(3) receptor ubiquitination. Thus, RNF170 plays an essential role in IP(3) receptor processing via the ubiquitin-proteasome pathway. |
| Databáze: | OpenAIRE |
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