| Induced in response to unfolded protein accumulation in the ER. UPR counteracts the harmful effect of unfolded proteins and promotes ER homeostasis (Schröder and Kaufman, 2005; Ron and Walter, 2007). |
Activated in response to PAMPs. MSR counteracts the physiological consequences of infection or microbial detection, while promoting immune defenses (Woo et al, 2009; Goodall et al, 2010; Martinon et al, 2010; Clavarino et al, 2012a, 2012b) |
| UPR comprises three different signal cascades, including the PERK/ATF4, ATF6 and IRE1/XBP1 pathways (Schröder and Kaufman, 2005; Ron and Walter, 2007). |
MSR comprises at least the TRIF/ATF4 or PKR/ATF4 pathways, mostly without CHOP protein expression and can display some IRE1 activation in specific cells types (Clavarino et al, 2012a, 2012b) |
| Upregulation of Xbp1, Bip, Ero1, ERdj4 and p58IPK, as well as other ER chaperones, and induction of protein degradation pathways. CHOP transcription and synthesis are strongly induced (Lee et al, 2003; Schröder and Kaufman, 2005; Ron and Walter, 2007). Atf3 and Gadd34 are strongly induced and ATF4 is synthetized. |
No upregulation of Bip, Ero1, ERdj4 and p58IPK. Cell-type-dependent limited upregulation of Xbp1 (Martinon et al, 2010). CHOP induction is limited both transcriptionaly and translationaly. Atf3 and Gadd34 are strongly induced and ATF4 is synthetized. |
| Translation is temporarily arrested, but is reinitiated upon eIF2α dephosphorylation by GADD34 (Schröder and Kaufman, 2005; Ron and Walter, 2007). |
Protein translation activity is induced and can be regulated independently of eIF2α dephosphorylation (Clavarino et al, 2012a, 2012b). |
| Potential role in sterile inflammatory cytokine transcription, but no demonstrated action on type-I IFN expression (Deng et al, 2004; Hsu et al, 2004). |
The ATF4/GADD34 axis regulates cytokine expression both transcriptionally and translationally in a PKR- or TRIF-dependent manner. Correct type-I IFN expression requires GADD34 and XBP1 (Clavarino et al, 2012a, 2012b; Martinon et al, 2010). |
| Can be ROS dependent (Hetz, 2012). |
Can be ROS independent (Li et al, 2010; Martinon et al, 2010). |
