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. 2019 Nov 9;20(22):5606. doi: 10.3390/ijms20225606

Figure 2.

Figure 2

The molecular mechanisms of endoplasmic reticulum-associated degradation (ERAD) and cross-presentation (CP). The processing of exogenous proteins in CP involves a part of the molecular machinery of ERAD; however, significant differences exist. ERAD is carried out in the ER, while ERAD-dependent antigen processing during CP takes place in the non-classical endosomes, together with ER-resident molecules. The recognition of unfolded proteins by ER-resident molecules is similar in both processes, except for the EDEMs. Both the HRD1 and the Sec61 complexes are utilized in ERAD, but the HRD1 complex is not essential for CP. Additionally, several kinds of ERAD-related molecules, such as E3s, cofactors of VCP (i.e., NPL4 and UFD1), co-chaperones of Hsp70 (i.e., Bag6), deglycosidase, and deubiquitinase, play an important role in ERAD but are not investigated in CP. Solid arrows indicate mechanisms supported by experimental evidence. Dashed arrows indicate hypothetical mechanisms that still lack experimental evidence.