BAG-6 is essential for selective elimination of defective proteasomal substrates.
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.
Minami
Ryosuke
R
Department of Biological Sciences, Tokyo Metropolitan University, Tokyo, Japan.
Hayakawa
Atsuko
A
Kagawa
Hiroki
H
Yanagi
Yuko
Y
Yokosawa
Hideyoshi
H
Kawahara
Hiroyuki
H
D000595:Amino Acid Sequence; D000818:Animals; D005805:Genes, MHC Class I; D006367:HeLa Cells; D006801:Humans; D008285:Major Histocompatibility Complex; D051379:Mice; D018832:Molecular Chaperones / Q000235:genetics / Q000378:metabolism*; D008969:Molecular Sequence Data; D041681:NIH 3T3 Cells; D010455:Peptides / Q000235:genetics / Q000378:metabolism*; D025821:Polyubiquitin / Q000378:metabolism; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism*; D011500:Protein Synthesis Inhibitors / Q000378:metabolism; D011691:Puromycin; D034741:RNA, Small Interfering / Q000235:genetics / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D014018:Tissue Distribution
C092009:BAG6 protein, human; D018832:Molecular Chaperones; D010455:Peptides; D011500:Protein Synthesis Inhibitors; D034741:RNA, Small Interfering; D011993:Recombinant Fusion Proteins; D025821:Polyubiquitin; D011691:Puromycin; D046988:Proteasome Endopeptidase Complex; C061553:ATP dependent 26S protease