Figure 3.

Retrotranslocation and degradation of ERAD substrates. (A) Proteins targeted for degradation by ERAD complex are retrotranslocated through a “retrotranlocon” (Hrd1, Doa10, and Sec61 are proposed to serve this role but only the E3s are shown for simplicity) with the mechanical force provided by the Cdc48-Npl4-Ufd1 AAA-ATPase complex. Polypeptides are subsequently ubiquitinated as depicted. (B) In the cytosol, Png1 removes N-linked glycans from substrates. Ufd2 can lengthen ubiquitin chains for some substrates. Polyubiquitinated species are recognized by Rad23p and passed to the proteasome for degradation.