BAG-6 is essential for selective elimination of defective proteasomal substrates

J Cell Biol. 2010 Aug 23;190(4):637-50. doi: 10.1083/jcb.200908092. Epub 2010 Aug 16.


BAG-6/Scythe/BAT3 is a ubiquitin-like protein that was originally reported to be the product of a novel gene located within the human major histocompatibility complex, although the mechanisms of its function remain largely obscure. Here, we demonstrate the involvement of BAG-6 in the degradation of a CL1 model defective protein substrate in mammalian cells. We show that BAG-6 is essential for not only model substrate degradation but also the ubiquitin-mediated metabolism of newly synthesized defective polypeptides. Furthermore, our in vivo and in vitro analysis shows that BAG-6 interacts physically with puromycin-labeled nascent chain polypeptides and regulates their proteasome-mediated degradation. Finally, we show that knockdown of BAG-6 results in the suppressed presentation of MHC class I on the cell surface, a procedure known to be affected by the efficiency of metabolism of defective ribosomal products. Therefore, we propose that BAG-6 is necessary for ubiquitin-mediated degradation of newly synthesized defective polypeptides.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Genes, MHC Class I
  • HeLa Cells
  • Humans
  • Major Histocompatibility Complex
  • Mice
  • Molecular Chaperones / genetics
  • Molecular Chaperones / metabolism*
  • Molecular Sequence Data
  • NIH 3T3 Cells
  • Peptides / genetics
  • Peptides / metabolism*
  • Polyubiquitin / metabolism
  • Proteasome Endopeptidase Complex / metabolism*
  • Protein Synthesis Inhibitors / metabolism
  • Puromycin
  • RNA, Small Interfering / genetics
  • RNA, Small Interfering / metabolism
  • Recombinant Fusion Proteins / genetics
  • Recombinant Fusion Proteins / metabolism
  • Tissue Distribution


  • BAG6 protein, human
  • Molecular Chaperones
  • Peptides
  • Protein Synthesis Inhibitors
  • RNA, Small Interfering
  • Recombinant Fusion Proteins
  • Polyubiquitin
  • Puromycin
  • Proteasome Endopeptidase Complex
  • ATP dependent 26S protease