Table 1.
ER chaperones and molecular components of the UPR.
| Protein/Gene | Function(s) | Reference |
|---|---|---|
| ER stress sensors | ||
| Bip (GRP78)/HSPA5 | Dissociation with ER stress sensors activates the UPR | (Bertolotti et al., 2000; Ng et al., 1992) |
| IRE1/ERN1 | Splices the mRNA encoding XBP1 to activate XBP1 Mediates degradation of ER-targeted mRNA (RIDD) Binds to TRAF2 and activates pathways of Ask1/JNK and IKK/NF-κB |
(Hollien et al., 2009; Urano et al., 2000; Yoshida et al., 2001) |
| PERK/EIF2AK3 | Phosphorylates eIF2α to downregulate global protein translation | (Harding et al., 2000) |
| ATF6/ATF6 | Activated in Golgi apparatus and upregulates ER-targeted genes | (Chen, 2002) |
| Transcription factors | ||
| XBP1/XBP1 | Induces ER chaperones (Bip, p58IPK, ERdj4, HEDJ, PDI-P5, EDEM, etc) Regulates other UPR genes (ATF6 and CHOP) Regulates genes in ER biogenesis Regulates oxidative stress, immune response and lipogenesis |
(Glimcher, 2010; Lee, 2002; Reimold, 2000; Zhong et al., 2012) |
| ATF6/ATF6 | Regulates UPR genes (XBP1, BIP/GRP78, CHOP) Regulates proteins involved in ERAD |
(Yamamoto et al., 2007; Yoshida et al., 2000) |
| ATF4/ATF4 | Induces pro-apoptotic gene CHOP Regulates stress response genes Regulates genes in oxidative stress and angiogenesis |
(Harding et al., 2003; Lange et al., 2008; Roybal et al., 2004) |
| CHOP/DDIT3 | Regulates pro- and anti-apoptotic genes and initiates apoptosis Induces eIF2α dephosphorylation via upregulation of GADD34 |
(Marciniak SJ, 2004; McCullough et al., 2001) |
| CREBH/CREBH | Activates acute-phase genes and regulates inflammatory response | (Zhang et al., 2006) |
| Regulator of protein translation | ||
| eIF-2α/EIF2A | Inhibits eIF2B to arrest general protein translation Increases translation of ATF4 and CHOP during ER stress |
(Harding et al., 1999; Ron and Walter, 2007) |
| ER Chaperones | ||
| Bip (GRP78)/HSPA5 | Binds unfolded or misfolded proteins and promotes protein folding/refolding | (Ting and Lee, 1988) |
| Calnexin/CANX | Recognizes oligosaccharide and promotes glycosylated protein folding | (Ware et al., 1995) |
| Calreticulin/CALR | promotes glycosylated protein folding and quality control Binds to calcium and functions as calcium buffering chaperone in ER |
(Michalak et al., 1999) |
| PDI/PDIA2 | Catalyzes disulfide bond formation | (Hatahet and Ruddock, 2009) |
| ERdj5/ERdj5 | Functions as a disulfide reductase to degrade misfolded proteins in the ER | (Ushioda et al., 2008) |