Figure 3.

(a) Cotranslational translocation of proteins occurs via the Sec61 translocon and is mediated in a BiP-dependent way either in the absence or presence of ERdj2, depending on the respective target protein. Cotranslational degradation of a target proteins is controlled by ERdj6. The retrotranslocation of targets that clog the translocon is BiP-dependent. (b) The degradation of luminal target proteins is mediated by ERdj3, ERdj4, and ERdj5. ERdj3 seems to compete with target proteins for the binding of calnexin or calreticulin and controls the degradation or folding of proteins. ERdj4 also mediates either the folding of proteins or, in the case of enduring misfolding, targets the protein to the ERAD pathway. The specific feature of ERdj5 is its reductive ability, required to release disulifide bonds in order to enable a subsequent retrotranslocation across the ER membrane.