Caught in the middle: the role of Bag3 in disease.
Bag3 is a Bag family co-chaperone that regulates the ATPase activity of Hsp70 (heat-shock protein 70) chaperones. Recent studies have demonstrated that Bag3 can initiate macroautophagy in co-operation with small heat-shock protein HspB8. In this issue of the Biochemical Journal, Fuchs and co-workers have discovered the IPV motif in Bag3 that is necessary for binding to HspB8. The authors have also identified HspB6 as a new binding partner for Bag3 and characterized further the binding of both HspB8 and HspB6 in Bag3-mediated clearance of aggregated polyglutamine-containing protein Htt43Q (huntingtin exon 1 fragment with 43 CAG repeats). It is clear from recent identification of a Bag3 mutation that causes a form of muscular dystrophy that the full function of Bag3 in disease is not clear. We will apply the findings of Fuchs et al. in this issue to reconcile the phenotypes of Bag3 homologue knockouts with the emerging role of Bag3 in autophagy.
McCollum
Andrea K
AK
Molecular Signaling Section, Medical Oncology Branch, National Cancer Institute, 9000 Rockville Pike, Bethesda, MD 20892, USA. mccollumak@mail.nih.gov
Casagrande
Giovanna
G
Kohn
Elise C
EC
D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics / Q000378:metabolism*; D051017:Apoptosis Regulatory Proteins; D001343:Autophagy; D001665:Binding Sites; D002460:Cell Line; D050886:HSP20 Heat-Shock Proteins / Q000235:genetics / Q000378:metabolism*; D006360:Heat-Shock Proteins / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D000071058:Huntingtin Protein; D008954:Models, Biological; D018832:Molecular Chaperones / Q000235:genetics / Q000378:metabolism; D009136:Muscular Dystrophies / Q000235:genetics / Q000378:metabolism; D009154:Mutation; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism; D011485:Protein Binding; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism*; D018911:Trinucleotide Repeats / Q000235:genetics
D048868:Adaptor Proteins, Signal Transducing; D051017:Apoptosis Regulatory Proteins; C414431:BAG3 protein, human; D050886:HSP20 Heat-Shock Proteins; C494382:HSPB6 protein, human; C413214:HSPB8 protein, human; C086055:HTT protein, human; D006360:Heat-Shock Proteins; D000071058:Huntingtin Protein; D018832:Molecular Chaperones; D009419:Nerve Tissue Proteins; D009687:Nuclear Proteins; D017346:Protein Serine-Threonine Kinases