Co-chaperone HSJ1a dually regulates the proteasomal degradation of ataxin-3.
Homo sapiens J domain protein (HSJ1) is a J-domain containing co-chaperone that is known to stimulate ATPase activity of HSP70 chaperone, while it also harbors two ubiquitin (Ub)-interacting motifs (UIMs) that may bind with ubiquitinated substrates and potentially function in protein degradation. We studied the effects of HSJ1a on the ... protein levels of both normal and the disease--related polyQ-expanded forms of ataxin-3 (Atx3) in cells. The results demonstrate that the N-terminal J-domain and the C-terminal UIM domain of HSJ1a exert opposite functions in regulating the protein level of cellular overexpressed Atx3. This dual regulation is dependent on the binding of the J-domain with HSP70, and the UIM domain with polyUb chains. The J-domain down-regulates the protein level of Atx3 through HSP70 mediated proteasomal degradation, while the UIM domain may alleviate this process via maintaining the ubiquitinated Atx3. We propose that co-chaperone HSJ1a orchestrates the balance of substrates in stressed cells in a Yin-Yang manner.
Mesh Terms:
Blotting, Western, Cells, Cultured, HSP40 Heat-Shock Proteins, HSP70 Heat-Shock Proteins, Humans, Immunoenzyme Techniques, Immunoprecipitation, Kidney, Molecular Chaperones, Nerve Tissue Proteins, Nuclear Proteins, Proteasome Endopeptidase Complex, Protein Binding, Protein Structure, Tertiary, Repressor Proteins, Ubiquitin, Ubiquitin-Protein Ligases
Blotting, Western, Cells, Cultured, HSP40 Heat-Shock Proteins, HSP70 Heat-Shock Proteins, Humans, Immunoenzyme Techniques, Immunoprecipitation, Kidney, Molecular Chaperones, Nerve Tissue Proteins, Nuclear Proteins, Proteasome Endopeptidase Complex, Protein Binding, Protein Structure, Tertiary, Repressor Proteins, Ubiquitin, Ubiquitin-Protein Ligases
PLoS ONE
Date: Jun. 01, 2011
PubMed ID: 21625540
View in: Pubmed Google Scholar
Download Curated Data For This Publication
135427
Switch View:
- Interactions 4
- PTM Genes 1