期刊
JOURNAL OF BIOLOGICAL CHEMISTRY
卷 286, 期 27, 页码 24426-24433出版社
AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
DOI: 10.1074/jbc.M111.251983
关键词
-
资金
- National Institutes of Health [DK049194]
Inositol 1,4,5-trisphosphate (IP3) receptors are endoplasmic reticulum membrane calcium channels that, upon activation, are degraded via the ubiquitin-proteasome pathway. While searching for novel mediators of IP3 receptor processing, we discovered that RNF170, an uncharacterized RING domain-containing protein, associates rapidly with activated IP3 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 IP3 receptor ubiquitination, and degradation and overexpression of a catalytically inactive RNF170 mutant suppressed stimulus-induced IP3 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 IP3 receptors immediately after their activation. Depletion of RNF170 did not affect the binding of the erlin1/2 complex to stimulated IP3 receptors, whereas erlin1/2 complex depletion inhibited RNF170 binding. These results suggest a model in which the erlin1/2 complex recruits RNF170 to activated IP3 receptors where it mediates IP3 receptor ubiquitination. Thus, RNF170 plays an essential role in IP3 receptor processing via the ubiquitin-proteasome pathway.
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