Figure 8.

ERAD and ER exit can compete for misfolded substrates. (A) Misfolded proteins lacking ER exit signals remain in the ER and are degraded by ERAD. (B) Misfolded proteins with intact ER exit signals are engaged by ERAD machinery for dislocation and proteasomal degradation. However, these misfolded proteins can also exit the ER via interaction with ER exit receptors (for soluble substrates) or via direct interaction of cytosolic signals with COPII components (for membrane-spanning substrates). (C) Inactivating ERAD results in greater ER exit of misfolded proteins containing ER export signals.