Nuclear export of ubiquitinated proteins via the UBIN-POST system

Proc Natl Acad Sci U S A. 2018 May 1;115(18):E4199-E4208. doi: 10.1073/pnas.1711017115. Epub 2018 Apr 16.

Abstract

Although mechanisms for protein homeostasis in the cytosol have been studied extensively, those in the nucleus remain largely unknown. Here, we identified that a protein complex mediates export of polyubiquitinated proteins from the nucleus to the cytosol. UBIN, a ubiquitin-associated (UBA) domain-containing protein, shuttled between the nucleus and the cytosol in a CRM1-dependent manner, despite the lack of intrinsic nuclear export signal (NES). Instead, the UBIN binding protein polyubiquitinated substrate transporter (POST) harboring an NES shuttled UBIN through nuclear pores. UBIN bound to polyubiquitin chain through its UBA domain, and the UBIN-POST complex exported them from the nucleus to the cytosol. Ubiquitinated proteins accumulated in the cytosol in response to proteasome inhibition, whereas cotreatment with CRM1 inhibitor led to their accumulation in the nucleus. Our results suggest that ubiquitinated proteins are exported from the nucleus to the cytosol in the UBIN-POST complex-dependent manner for the maintenance of nuclear protein homeostasis.

Keywords: protein aggregation; protein quality control; protein transport; ubiquitin.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Active Transport, Cell Nucleus / physiology
  • Animals
  • Carrier Proteins / genetics
  • Carrier Proteins / metabolism*
  • Cell Nucleus / genetics
  • Cell Nucleus / metabolism*
  • Cytosol / metabolism*
  • HEK293 Cells
  • HeLa Cells
  • Human Umbilical Vein Endothelial Cells / cytology
  • Human Umbilical Vein Endothelial Cells / metabolism*
  • Humans
  • Membrane Proteins / genetics
  • Membrane Proteins / metabolism*
  • Mice
  • NIH 3T3 Cells
  • Nuclear Proteins / genetics
  • Nuclear Proteins / metabolism*
  • Solute Carrier Proteins
  • Ubiquitinated Proteins / genetics
  • Ubiquitinated Proteins / metabolism*

Substances

  • Carrier Proteins
  • Membrane Proteins
  • Nuclear Proteins
  • SLC35G1 protein, human
  • Solute Carrier Proteins
  • UBQLN4 protein, human
  • Ubiquitinated Proteins