Ubiquitin-specific protease 8 deubiquitinates Sec31A and decreases large COPII carriers and collagen IV secretion

Biochem Biophys Res Commun. 2018 May 15;499(3):635-641. doi: 10.1016/j.bbrc.2018.03.202. Epub 2018 Mar 31.


Nascent cargo proteins in the endoplasmic reticulum are transported to the Golgi by COPII carriers. Typical COPII vesicles are 60-70 nm in diameter, and much larger macromolecules, such as procollagen, are transported by atypical large COPII carriers in mammalian cells. The formation of large COPII carriers is enhanced by Cul3 ubiquitin ligase, which mono-ubiquitinates Sec31A, a COPII coat protein. However, the deubiquitinating enzyme for Sec31A was unclear. Here, we show that the deubiquitinating enzyme USP8 interacts with and deubiquitinates Sec31A. The interaction was mediated by the adaptor protein STAM1. USP8 overexpression inhibited the formation of large COPII carriers. By contrast, USP8 knockdown caused the accumulation of COPII coat proteins around the cis-Golgi, promoted the intracellular trafficking of procollagen IV from the endoplasmic reticulum to the Golgi, and increased collagen IV secretion. We concluded that USP8 deubiquitinates Sec31A and inhibits the formation of large COPII carriers, thereby suppressing collagen IV secretion.

Keywords: COPII; Collagen; Deubiquitination; STAM; USP8; Ubiquitin.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptor Proteins, Signal Transducing / metabolism
  • Animals
  • COP-Coated Vesicles / metabolism*
  • Cell Line
  • Collagen Type IV / metabolism*
  • Endopeptidases / metabolism*
  • Endosomal Sorting Complexes Required for Transport / metabolism*
  • Humans
  • Intracellular Space / metabolism
  • Phosphoproteins / metabolism
  • Protein Binding
  • Ubiquitin Thiolesterase / metabolism*
  • Ubiquitination*
  • Vesicular Transport Proteins / metabolism*


  • Adaptor Proteins, Signal Transducing
  • Collagen Type IV
  • Endosomal Sorting Complexes Required for Transport
  • Phosphoproteins
  • SEC31A protein, human
  • STAM protein, human
  • Vesicular Transport Proteins
  • Endopeptidases
  • USP8 protein, human
  • Ubiquitin Thiolesterase