Ron and Habener (1992) identified a nuclear protein that serves as a dominant-negative inhibitor of the transcription
factors C/EBP (OMIM:116897, 116898) and LAP (OMIM:189965). The protein was called CHOP for C/EBP-homologous protein but
is also referred to as DDIT3 for 'DNA damage-inducible transcript 3' and GADD153 for 'growth arrest- and DNA
damage-inducible gene.' They found that bacterially expressed CHOP inhibits the DNA-binding activity of C/EBP and
LAP by forming heterodimers that cannot bind DNA.
NCBI Summary:
This gene encodes a member of the CCAAT/enhancer-binding protein (C/EBP) family of transcription factors. The protein functions as a dominant-negative inhibitor by forming heterodimers with other C/EBP members, such as C/EBP and LAP (liver activator protein), and preventing their DNA binding activity. The protein is implicated in adipogenesis and erythropoiesis, is activated by endoplasmic reticulum stress, and promotes apoptosis. Fusion of this gene and FUS on chromosome 16 or EWSR1 on chromosome 22 induced by translocation generates chimeric proteins in myxoid liposarcomas or Ewing sarcoma. Multiple alternatively spliced transcript variants encoding two isoforms with different length have been identified. [provided by RefSeq, Aug 2010]
General function
Cell death/survival, Cell cycle regulation, DNA Replication, Nucleic acid binding, DNA binding, Transcription factor
Comment
Cellular localization
Nuclear, ER
Comment
Ovarian function
Oogenesis, Oocyte maturation
Comment
Gene whose expression is detected by cDNA array hybridization: GDP/GTP exchangers, GTPase stimulators and inhibitors, apoptosis Rozenn Dalbis-Tran and Pascal Mermilloda
Expression regulated by
FSH
Comment
Ovarian localization
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.//////////////////
Fontanier-Razzaq N, et al 2001 reported that DNA damaging agents increase gadd153 (CHOP-10) messenger RNA
levels in bovine preimplantation embryos cultured in vitro.
DNA damage and other forms of stress are believed to be important factors in
reducing the efficiency of in vitro embryo transfer techniques in farm animals. The expression of mRNAs from stress-responsive genes such as gadd153
(CHOP-10, ddit3) may provide a means of assessing the quality of embryos produced in vitro. Treatment of bovine granulosa cell cultures with the
DNA-damaging agents, methyl methane-sulphonate (MMS) or sodium arsenite,
induced the expression of an mRNA, which hybridized with the hamster gadd153
cDNA.