UPR signalling pathway

UPR signalling pathway. The three ER‐resident transmembrane proteins, ATF6, IRE1 and PERK, associate with Bip in their inactive state under normal condition. In response to ER stress, these sensors are released and activated. Both IRE1 and PERK are oligomerized and autophosphorylated. Phosphorylated IRE1 catalyses the splicing of XBP1 mRNA leading to the generation of UPR‐target transcription factor. Activated PERK phosphorylates eIF2α leading to general translational attenuation and increased expression of ATF4. ATF6 is cleaved by SP1/SP2, and the cytosolic fragment of ATF6 migrates to the nucleus. The downstream effectors of these three signalling pathways, in combination, induce the expression of proteins, which can help restore the ER protein folding capacity. ERAD is accelerated to remove terminally misfolded proteins.
UPR signalling pathway
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Publication

Endoplasmic reticulum stress in the heart: insights into mechanisms and drug targets. (2018) Shunyao Wang, et al. Br J Pharmacol. 2018 Apr;175(8):1293-1304. Figure: F1.

Gene mentions


Organism Group Word Match Source NCBI Symbol NCBI ID
Danio rerio Vertebrates (SP1 SP1 ncbigene_symbol sp1 324109
Danio rerio Vertebrates (SP1/SP2) SP2 ncbigene_symbol sp2 556835
Danio rerio Vertebrates (SP1/SP2) SP2 ncbigene_synonym nenf 571299
Danio rerio Vertebrates elF2a ELF2A ncbigene_symbol elf2a 445489
Danio rerio Vertebrates elF2a EIF2A ncbigene_symbol eif2a 573991
Danio rerio Vertebrates ATF4 ATF4 ncbigene_synonym atf4a 406514
Danio rerio Vertebrates XBP-1 XBP1 ncbigene_symbol xbp1 140614
Homo sapiens Primates Bip BIP ncbigene_synonym GDF10 2662
Homo sapiens Primates Bip BIP ncbigene_synonym HSPA5 3309
Homo sapiens Primates ATF6a ATF6A ncbigene_synonym ATF6 22926
Homo sapiens Primates PERK PERK ncbigene_synonym EIF2AK3 9451
Homo sapiens Primates (SP1 SP1 ncbigene_symbol SP1 6667
Homo sapiens Primates (SP1 SP1 ncbigene_synonym PSG1 5669
Homo sapiens Primates (SP1 SP1 ncbigene_synonym DAND5 199699
Homo sapiens Primates (SP1/SP2) SP2 ncbigene_symbol SP2 6668
Homo sapiens Primates (SP1/SP2) SP2 ncbigene_synonym SPATA1 100505741
Homo sapiens Primates ХВР-1 XBP-1 ncbigene_synonym XBP1 7494
Homo sapiens Primates elF2a EIF2A ncbigene_symbol EIF2A 83939
Homo sapiens Primates elF2a EIF2A ncbigene_synonym EIF2S1 1965
Homo sapiens Primates ATF4 ATF4 ncbigene_symbol ATF4 468
Homo sapiens Primates CHOP CHOP ncbigene_synonym DDIT3 1649

Chemical mentions

Word Match MeSH Name ChEBI

Disease mentions

Word Match MeSH Name DOID