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Ovarian Kaleidoscope Database (OKdb)

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activating transcription factor 6 OKDB#: 2458
 Symbols: ATF6 Species: human
 Synonyms: ACHM7, ATF6A  Locus: 1q23.3 in Homo sapiens


For retrieval of Nucleotide and Amino Acid sequences please go to: OMIM Entrez Gene
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General Comment

NCBI Summary: This gene encodes a transcription factor that activates target genes for the unfolded protein response (UPR) during endoplasmic reticulum (ER) stress. Although it is a transcription factor, this protein is unusual in that it is synthesized as a transmembrane protein that is embedded in the ER. It functions as an ER stress sensor/transducer, and following ER stress-induced proteolysis, it functions as a nuclear transcription factor via a cis-acting ER stress response element (ERSE) that is present in the promoters of genes encoding ER chaperones. This protein has been identified as a survival factor for quiescent but not proliferative squamous carcinoma cells. There have been conflicting reports about the association of polymorphisms in this gene with diabetes in different populations, but another polymorphism has been associated with increased plasma cholesterol levels. This gene is also thought to be a potential therapeutic target for cystic fibrosis. [provided by RefSeq, Aug 2011]
General function Nucleic acid binding, DNA binding, Transcription factor
Comment
Cellular localization Nuclear
Comment
Ovarian function Steroid metabolism
Comment ATF6 knock-down decreases apoptosis, arrests the S phase of the cell cycle and increases steroid hormone production in mouse granulosa cells. Xiong Y et al. (2017) Activating transcription factor 6 (ATF6) is an important factor in the endoplasmic reticulum (ER) stress signaling pathway. The aim of this study was to assess the role of ATF6 in mouse granulosa cells with respect to apoptosis, the cell cycle, and steroid hormone production, as well as several key genes related to follicular development, via RNA interference, immunohistochemical staining, real-time quantitative polymerase chain reaction, western blotting, flow cytometry, TUNEL assay, and ELISA. Immunohistochemical staining revealed that ATF6 was extensively distributed in the granulosa cells of various ovarian follicles and oocytes in adult female mice. FSH or LH treatment significantly increased ATF6 protein levels .Flow cytometry and TUNEL assays analysis indicated that ATF6 depletion decreased apoptosis and arrested the S-phase of cell cycle. Consistent with these results, p53, Caspase-3, Bax, Chop, CyclinA1, CyclinB1, and CyclinD2 mRNA expression decreased, whereas Bcl-2 and Grp78 mRNA expression increased. Interestingly, ATF6 knock-down obviously increased progesterone and estradiol production. Cyp1b1 mRNA levels were down-regulated, whereas Cyp11a1, Star and Cyp19a1 mRNA levels were up-regulated, in keeping with the changes in steroid hormones. Furthermore, ATF6 disruption remarkably increased Igfbp4 expression and decreased Has2, Ptgs2 and Ptgfr expression. But after treating with tunicamycin (Tm), the levels of Has2, Ptgs2 and Ptgfr increased relatively whereas Igfbp4 expression decreased. Collectively, these results imply that ATF6 may regulate apoptosis, the cell cycle, steroid hormone synthesis, and other modulators related to folliculogenesis, which may indirectly involve in the development, ovulation, and atresia of ovarian follicles by affecting the physiological function of granulosa cells.//////////////////
Expression regulated by FSH
Comment
Ovarian localization Oocyte, Granulosa
Comment Cross-Talk Between FSH and Endoplasmic Reticulum Stress: A Mutually Suppressive Relationship. Babayev E et al. (2015) Suboptimal cellular conditions result in the accumulation of unfolded proteins in the endoplasmic reticulum (ER) and trigger ER stress. In this study, we investigated the effects of follicle stimulating hormone (FSH) on ER stress in granulosa cells (GCs) obtained from 3-week-old female C57BL6 mice 24 or 48 hours after intraperitoneal injection of 5 IU pregnant mare's serum gonadotropin (PMSG), and in primary mouse GCs in culture treated with FSH (10-100 mIU/mL) for 24 or 48 hours. Moreover, mouse GCs in culture were treated with tunicamycin (Tm) or thapsigargin (Tp), which induce ER stress by inhibiting N-glycosylation of ER proteins and ER calcium adenosine triphosphatase, respectively, and their response to FSH was evaluated. We found that FSH attenuated ER stress in mouse GCs in vivo and in vitro; messenger RNA levels of ER stress-associated genes Xbp1s, Atf6, Chop, and Casp12 were decreased upon exposure to FSH/PMSG. Activating transcription factor 4 protein levels also demonstrated consistent decrease following FSH stimulation. Both Tm and Tp treatments inhibited FSH response, ER stress-induced cells did not show any change in estradiol levels in response to FSH, whereas in untreated GCs, estradiol production increased 3-fold after incubation with FSH for 60 hours. Furthermore, ER stress-induced cells failed to demonstrate aromatase (Cyp19a1) expression upon exposure to FSH. Importantly, under high-ER stress conditions FSH stimulation was unable to downregulate the expression of ER stress-associated genes. Our findings suggest that FSH decreases ER stress in GCs under physiologic conditions. However, under conditions that cause a significant increase in ER stress, FSH response is attenuated.////////////////// Zheng P, et al compared the temporal expression patterns of five housekeeping mRNAs and three transcription factor mRNAs between mouse and rhesus monkey.
Follicle stages
Comment
Phenotypes
Mutations 0 mutations
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created: April 23, 2004, 7:19 p.m. by: hsueh   email:
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last update: Jan. 23, 2017, 12:53 p.m. by: hsueh    email:



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