Distinct proteostasis circuits cooperate in nuclear and cytoplasmic protein quality control.

ABSTRACT: Protein misfolding is linked to a wide array of human disorders, including Alzheimer's disease, Parkinson's disease and type II diabetes^1,2. Protective cellular protein quality control (PQC) mechanisms have evolved to selectively recognize misfolded proteins and limit their toxic effects^3-9, thus contributing to the maintenance of the proteome (proteostasis). Here we examine how molecular chaperones and the ubiquitin-proteasome system cooperate to recognize and promote the clearance of soluble misfolded proteins. Using a panel of PQC substrates with distinct characteristics and localizations, we define distinct chaperone and ubiquitination circuitries that execute quality control in the cytoplasm and nucleus. In the cytoplasm, proteasomal degradation of misfolded prot

SUBMITTER: Samant RS 

PROVIDER: S-EPMC6707801 | biostudies-literature | 2018 Nov

REPOSITORIES: biostudies-literature