Target type: biologicalprocess
Any process that modulates the frequency, rate or extent of the IRE1-mediated unfolded protein response. [GO_REF:0000058, GOC:bf, GOC:PARL, GOC:TermGenie, PMID:22013210]
The unfolded protein response (UPR) is a cellular stress response that is activated when unfolded or misfolded proteins accumulate in the endoplasmic reticulum (ER). The UPR aims to restore ER homeostasis by reducing protein translation, increasing protein folding capacity, and degrading misfolded proteins. IRE1 is one of the three major UPR sensors, alongside PERK and ATF6.
IRE1, an ER transmembrane protein, possesses both kinase and endoribonuclease activities. Upon accumulation of misfolded proteins, IRE1 oligomerizes and autophosphorylates. This activation triggers its endoribonuclease activity, which splices the mRNA encoding the transcription factor XBP1. The spliced XBP1 mRNA encodes a highly active transcription factor, XBP1s, which translocates to the nucleus and initiates the transcription of genes involved in protein folding, ER-associated protein degradation (ERAD), and lipid biosynthesis.
IRE1 also activates the downstream signaling pathway by cleaving a specific mRNA, leading to the production of a transcription factor called ATF6. ATF6 promotes the expression of genes involved in the UPR, such as chaperones and ERAD components.
In addition to splicing XBP1 mRNA, IRE1 can also activate the downstream signaling pathway through another mechanism: the regulated IRE1-dependent decay (RIDD). This process involves the degradation of specific mRNAs encoding ER-resident proteins. The degradation of these mRNAs reduces the load of proteins entering the ER, thereby alleviating stress.
IRE1-mediated UPR plays a crucial role in maintaining ER homeostasis and cell survival. However, chronic or prolonged activation of IRE1 can lead to cell death. Therefore, the regulation of IRE1 activity is critical for cell survival and function.'
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| Protein | Definition | Taxonomy |
|---|---|---|
| COP9 signalosome complex subunit 5 | A COP9 signalosome complex subunit 5 that is encoded in the genome of human. [PRO:DNx, UniProtKB:Q92905] | Homo sapiens (human) |
| Endoplasmic reticulum chaperone BiP | An endoplasmic reticulum chaperone BiP that is encoded in the genome of human. [PRO:DAN] | Homo sapiens (human) |
| Compound | Definition | Classes | Roles |
|---|---|---|---|
| dichlorophen | Dichlorophen: Nontoxic laxative vermicide effective for taenia infestation. It tends to produce colic and nausea. It is also used as a veterinary fungicide, anthelmintic, and antiprotozoan. (From Merck, 11th ed.) | bridged diphenyl fungicide; diarylmethane | |
| hexachlorophene | hexachlorophene : An organochlorine compound that is diphenylmethane in which each of the phenyl groups is substituted by chlorines at positions 2, 3, and 5, and by a hydroxy group at position 6. An antiseptic that is effective against Gram-positive organisms, it is used in soaps and creams for the treatment of various skin disorders. It is also used in agriculture as an acaricide and fungicide, but is not approved for such use within the European Union. Hexachlorophene: A chlorinated bisphenol antiseptic with a bacteriostatic action against Gram-positive organisms, but much less effective against Gram-negative organisms. It is mainly used in soaps and creams and is an ingredient of various preparations used for skin disorders. (From Martindale, The Extra Pharmacopoeia, 30th ed, p797) | bridged diphenyl fungicide; polyphenol; trichlorobenzene | acaricide; antibacterial agent; antifungal agrochemical; antiseptic drug |
| triclosan | aromatic ether; dichlorobenzene; monochlorobenzenes; phenols | antibacterial agent; antimalarial; drug allergen; EC 1.3.1.9 [enoyl-[acyl-carrier-protein] reductase (NADH)] inhibitor; EC 1.5.1.3 (dihydrofolate reductase) inhibitor; fungicide; persistent organic pollutant; xenobiotic | |
| adenosine diphosphate | Adenosine Diphosphate: Adenosine 5'-(trihydrogen diphosphate). An adenine nucleotide containing two phosphate groups esterified to the sugar moiety at the 5'-position. | adenosine 5'-phosphate; purine ribonucleoside 5'-diphosphate | fundamental metabolite; human metabolite |
| 2,2'-methylenebis(ethyl-6-tert-butylphenol) | |||
| 2,2'-methylenebis(4-methyl-6-tert-butylphenol) | diarylmethane | ||
| oxyclozanide | Oxyclozanide: Anthelmintic used in grazing animals for fasciola and cestode infestations. | ||
| 2,2'-bisphenol f | 2,2'-bisphenol F: contact allergen; structure given in first source | diarylmethane | |
| 8-mercaptoquinoline | 8-mercaptoquinoline: structure given in first source | ||
| 8-aminoadenosine | |||
| ver 155008 | VER 155008: structure in first source | purine nucleoside |