Target type: biologicalprocess
Any process that modulates the frequency, rate or extent of the ATF6-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 activated by the accumulation of unfolded or misfolded proteins in the endoplasmic reticulum (ER). ATF6 is one of the three major signaling pathways of the UPR, alongside PERK and IRE1. ATF6 is a transmembrane protein that resides in the ER membrane.
When unfolded proteins accumulate in the ER lumen, they bind to chaperone proteins like BiP/GRP78, which normally keep ATF6 in an inactive state. This binding disrupts the association of BiP/GRP78 with ATF6, leading to its release and transport to the Golgi apparatus.
In the Golgi, ATF6 is cleaved by two proteases, S1P and S2P. This cleavage removes the transmembrane domain, releasing the cytosolic, N-terminal fragment of ATF6. This fragment, known as ATF6(N), translocates to the nucleus where it acts as a transcription factor.
ATF6(N) binds to specific DNA sequences known as ER stress response elements (ERSEs) in the promoters of target genes. These genes encode proteins involved in protein folding, ER chaperones, ER-associated degradation (ERAD), and other processes that help to alleviate ER stress.
ATF6(N) also activates the expression of XBP1 mRNA, which undergoes unconventional splicing by IRE1. The spliced form of XBP1 encodes a potent transcription factor that further enhances the UPR by upregulating genes involved in protein folding and ERAD.
The regulation of ATF6 activity is crucial for maintaining ER homeostasis. Upregulation of ATF6 is beneficial in the early stages of ER stress, as it helps to alleviate stress by increasing protein folding capacity and ERAD activity. However, prolonged activation of ATF6 can be detrimental, leading to apoptosis or cell death. Therefore, ATF6 activity must be tightly controlled to ensure the proper functioning of the UPR.'
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| Protein | Definition | Taxonomy |
|---|---|---|
| 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-aminoadenosine | |||
| ver 155008 | VER 155008: structure in first source | purine nucleoside |