ER-associated degradation

Chaperones. Figure 2 The multiple roles of BiP in the biogenesis of the secretory proteins. BiP, immunoglobulin heavy chain binding protein ER, endoplasmic reticulum ERAD, ER-associated degradation ERj, resident ER protein with J-domain Sec61, core subunit of the protein translocase UPR, unfolded protein response that involves several signal transduction pathways that are activated in order to increase the biosynthetic capacity and decrease the biosynthetic burden of the ER... 

ER-Associated Degradation, when proteins mis-fold in the ER due to mutation or environmental conditions, they are selectively exported to the cytosol for degradation by the proteasome. 

Bays, N. W., Gardner, R. G., Seelig, L. P., JoAZEiRO, C. A., and Hampton, R. Y. Hrdlp/Der3p is a membrane-anchored ubiquitin ligase required for ER-associated degradation. Nature Cell Biol. 2000, 3, 24-29. 

Travers, K. J., Path, C. K., Wodicka, L, Lockhart, D. J., Weissman, J. S., and Walter, P. Functional and genomic analyses reveal an essential coordination between the unfolded protein response and ER-associated degradation. Cell 2000, 101, 249-58. 

Hampton, R. Y. ER-associated degradation in protein quality control and cellular regulation. Curr Opin Cell Biol 2002, 34, 476-82. 

Ramos-Castaneda, J., Park, Y.N., Liu, M., Hauser, K., Rudolph, H., Shull, G.E., Jonkman, M.F., Mori, K., Ikeda, S., Ogawa, H., and Arvan, P., 2005, Deficiency of ATP2C1, a Golgi ion pump, induces secretory pathway defects in endoplasmic reticulum (ER)-associated degradation and sensitivity to ER stress. J. Biol. Chem. 280, 9467—9473... 

Fig. 12.3 The unfolded proteins in the endoplasmic reticulum turn on the unfolded protein response (UPR) and ER-associated degradation (ERAD). The presented model was adapted from McCracken and Brodsky [59]...

Oda, Y, Okada, T, Yoshida, H., Kaufman, R.J., Nagata, K. and Mori, K. (2006) Derlin-2 and Derlin-3 are regulated by the mammalian unfolded protein response and are required for ER-associated degradation. J. Cell Biol. 172, 383-393. 

Lederkremer, G.Z. Glycoprotein folding, quality control and ER-associated degradation. Curr. Opin. Struct. Biol. 2009,19, 515-23. 

Nakatsukasa, K., Huyer, G., Michaelis, S., and Brodsky, J.L. (2008) Dissecting the ER-associated degradation of a misfolded polytopic membrane protein. Cell, 132, 101-112. 

Lee, M.C., and Miller, E.A. (2007) Inhibiting endoplasmic reticulum (ER)-associated degradation of rnisfolded Yorlp does not permit ER export despite the presence of a diacidic sorting signal. Molecular Biology of the Cell, 18, 3398-3413. 

ER-associated degradation (ERAD) DERI, HRD1/DER3, HRD3, UBC7... 

B. Addition of antioxidants to cells treated with (co-3) fatty acids restored normal apo B secretion. Interestingly, the induction of ER stress, with glucosamine or over-expression of Grp78, also increased apo B degradation and decreased apo B secretion (K. Adeli, 2005). Indeed, ER stress mechanisms appear to lead to both post-ER pre-secretory proteolysis of apo B as well as proteasome-mediated ER-associated degradation (K. Adeli, 2006). 

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