BAG-1 associates with the polyglutamine-expanded huntingtin aggregates.
Huntington's disease (HD) is characterised by the proteolytic production of N-terminal fragments of huntingtin containing polyglutamine repeats that forms intracellular ubiquitinated aggregates in the affected neurons. Using cellular and transgenic mice model of HD, we report here that BAG-1 co-immunoprecipitates with the polyglutamine-expanded truncated N-terminal huntingtin (tNhtt) and associates with their aggregates through its interaction with the chaperones Hsc70/Hsp70. We further demonstrate that the over expression of BAG-1 protects polyglutamine-expanded tNhtt induced cell death. Since, BAG-1 is essential for cell survival, its association with tNhtt aggregates might disrupt its normal function and thereby promote polyglutamine-expanded tNhtt-induced cell death.
Jana
Nihar Ranjan
NR
Cellular and Molecular Neuroscience Laboratory, National Brain Research Centre, Manesar, Gurgaon 122050, India. nihar@nbrc.ac.in
Nukina
Nobuyuki
N
D000818:Animals; D001921:Brain / Q000378:metabolism* / Q000473:pathology; D002352:Carrier Proteins / Q000378:metabolism*; D016923:Cell Death / Q000502:physiology; D002460:Cell Line; D002470:Cell Survival / Q000502:physiology; D004268:DNA-Binding Proteins; D004195:Disease Models, Animal; D050883:HSC70 Heat-Shock Proteins; D018840:HSP70 Heat-Shock Proteins / Q000378:metabolism; D000071058:Huntingtin Protein; D006816:Huntington Disease / Q000378:metabolism* / Q000473:pathology; D002479:Inclusion Bodies / Q000378:metabolism; D046911:Macromolecular Substances; D051379:Mice; D008822:Mice, Transgenic; D009410:Nerve Degeneration / Q000378:metabolism* / Q000473:pathology; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D009687:Nuclear Proteins / Q000378:metabolism*; D010446:Peptide Fragments / Q000378:metabolism; D010455:Peptides / Q000378:metabolism*; D014157:Transcription Factors; D019680:Trinucleotide Repeat Expansion / Q000502:physiology
C091732:BCL2-associated athanogene 1 protein; D002352:Carrier Proteins; D004268:DNA-Binding Proteins; D050883:HSC70 Heat-Shock Proteins; D018840:HSP70 Heat-Shock Proteins; C494372:Hspa8 protein, mouse; C506812:Htt protein, mouse; D000071058:Huntingtin Protein; D046911:Macromolecular Substances; D009419:Nerve Tissue Proteins; D009687:Nuclear Proteins; D010446:Peptide Fragments; D010455:Peptides; D014157:Transcription Factors; C097188:polyglutamine