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CHN-1 and CHN-1 L141R interacting proteins

ABSTRACT: Proteostasis is achieved by quality control pathways that support the generation of correctly folded proteins, prevent protein misfolding and remove toxic proteins. The quality control E3 ligase CHIP ubiquitylates damaged proteins consigned by chaperone partners for disposal through the endo-lysosomal pathway, proteasomal degradation, or autophagy. Additionally, CHIP has been reported to modulate essential signaling pathways by precisely delivering a myriad of native proteins to destined fates. We aimed at understanding the substrate specificity and processivity through a “structure to function” approach, by examining the modeled 3D structure of the C. elegans ortholog of CHIP, CHN-1, based on the reported structure of murine CHIP. Using different model organisms and various genetic and biochemical analyses, we demonstrate that monomeric CHN-1/CHIP has preserved ubiquitylation activity and promotes longevity via the IIS pathway. The lack of monomer results in premature aging and neurodegenerative disorder. Our data reveal that autoubiquitylation plays an important role in the alteration between monomer and dimer. Together, the conserved dimer-monomer transition provides a molecular switch regulating CHIP activity in response to proteotoxic stress and aging.

INSTRUMENT(S): Q Exactive HF-X

ORGANISM(S): Caenorhabditis Elegans

SUBMITTER: Thorsten Hoppe

LAB HEAD: Thorsten Hoppe

PROVIDER: PXD025375 | Pride | 2022-08-25

REPOSITORIES: Pride

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Transcription factor binding in liver tissue isolated from WT and GRdim mice

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