Quality control of human ABCG2 protein in the endoplasmic reticulum: ubiquitination and proteasomal degradation

Adv Drug Deliv Rev. 2009 Jan 31;61(1):66-72. doi: 10.1016/j.addr.2008.08.008. Epub 2008 Dec 11.

Abstract

Human ATP-binding cassette (ABC) transporter ABCG2 (BCRP/MXR/ABCP) is a plasma membrane protein carrying intra- and inter-molecular disulfide bonds and an N-linked glycan. Both disulfide bond formation and N-glycosylation are critical check points determining the stability and degradation fate of ABCG2 protein in the endoplasmic reticulum (ER). Misfolded ABCG2 protein without those post-translational modifications is removed from the ER by retrotranslocation to the cytosol compartment, ubiquitination by ubiquitin ligase, and finally degradation by proteasomes. Certain non-synonymous SNP variants of ABCG2 undergo such ER-associated degradation (ERAD).

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • ATP Binding Cassette Transporter, Subfamily G, Member 2
  • ATP-Binding Cassette Transporters / chemistry
  • ATP-Binding Cassette Transporters / genetics
  • ATP-Binding Cassette Transporters / metabolism*
  • ATP-Binding Cassette Transporters / physiology*
  • Amino Acid Sequence
  • Animals
  • Endoplasmic Reticulum / metabolism*
  • Humans
  • Molecular Sequence Data
  • Neoplasm Proteins / chemistry
  • Neoplasm Proteins / genetics
  • Neoplasm Proteins / metabolism*
  • Neoplasm Proteins / physiology*
  • Polymorphism, Single Nucleotide
  • Proteasome Endopeptidase Complex / metabolism*
  • Protein Folding
  • Protein Processing, Post-Translational*
  • Protein Stability
  • Sequence Homology, Amino Acid
  • Ubiquitination*

Substances

  • ABCG2 protein, human
  • ATP Binding Cassette Transporter, Subfamily G, Member 2
  • ATP-Binding Cassette Transporters
  • Neoplasm Proteins
  • Proteasome Endopeptidase Complex