Substrate-specific translocational attenuation during ER stress defines a pre-emptive quality control pathway.

ABSTRACT: Eukaryotic proteins entering the secretory pathway are translocated into the ER by signal sequences that vary widely in primary structure. We now provide a functional rationale for this long-observed sequence diversity by demonstrating that differences among signals facilitate substrate-selective modulation of protein translocation. We find that during acute ER stress, translocation of secretory and membrane proteins is rapidly and transiently attenuated in a signal sequence-selective manner. Their cotranslational rerouting to the cytosol for degradation reduces the burden of misfolded substrates entering the ER and represents a pathway for pre-emptive quality control (pQC). Bypassing the pQC pathway for the prion protein increases its rate of aggregation in the ER lumen during prolonged s

SUBMITTER: Kang SW 

PROVIDER: S-EPMC3656606 | biostudies-literature | 2006 Dec

REPOSITORIES: biostudies-literature