Sec16A, a key protein in COPII vesicle formation, regulates the stability and localization of the novel ubiquitin ligase RNF183

PLoS One. 2018 Jan 4;13(1):e0190407. doi: 10.1371/journal.pone.0190407. eCollection 2018.

Abstract

We identified 37 ubiquitin ligases containing RING-finger and transmembrane domains. Of these, we found that RNF183 is abundantly expressed in the kidney. RNF183 predominantly localizes to the endoplasmic reticulum (ER), Golgi, and lysosome. We identified Sec16A, which is involved in coat protein complex II vesicle formation, as an RNF183-interacting protein. RNF183 colocalized with Sec16A and interacted through the central conserved domain (CCD) of Sec16A. Although Sec16A is not a substrate for RNF183, RNF183 was more rapidly degraded by the ER-associated degradation (ERAD) in the absence of Sec16A. Sec16A also stabilized the interacting ubiquitin ligase RNF152, which localizes to the lysosome and has structural similarity with RNF183. These results suggest that Sec16A appears to regulate the protein stability and localization of lysosomal ubiquitin ligases.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • COP-Coated Vesicles / metabolism*
  • Endoplasmic Reticulum / metabolism
  • Golgi Apparatus / metabolism
  • Humans
  • Lysosomes / metabolism
  • Ubiquitin-Protein Ligases / metabolism*
  • Vesicular Transport Proteins / physiology*

Substances

  • SEC16A protein, human
  • Vesicular Transport Proteins
  • RNF183 protein, human
  • Ubiquitin-Protein Ligases

Grant support

This study was supported by Grants-in-Aid for Science Research (KAKENHI) 17H06416, 15K21706, 26460099, 25251014, and 15K15067 from the Ministry of Education, Culture, Sports, Science and Technology, Japan (https://www.jsps.go.jp/english/e-grants/).