Activating transcription factor 3 is a member of the mammalian activation transcription factor/cAMP responsive element-binding (CREB) protein family of transcription factors. Multiple transcript variants encoding two different isoforms have been found for this gene. The longer isoform represses rather than activates transcription from promoters with ATF binding elements. The shorter isoform (deltaZip2) lacks the leucine zipper protein-dimerization motif and does not bind to DNA, and it stimulates transcription presumably by sequestering inhibitory co-factors away from the promoter. It is possible that alternative splicing of the ATF3 gene may be physiologically important in the regulation of target genes. [provided by RefSeq]
General function
Nucleic acid binding, DNA binding, Transcription factor
Comment
Cellular localization
Nuclear
Comment
Ovarian function
Steroid metabolism, Luteolysis
Comment
ATF3 Expression in the Corpus Luteum: Possible Role in Luteal Regression{dagger} Mao D 2013 et al.
The present study investigated the induction and possible role of activating transcription factor 3 (ATF3) in the corpus luteum. Postpubertal cattle were treated at midcycle with prostaglandin F2a(PGF) for 0-4 hours. Luteal tissue was processed for immunohistochemistry, in situ hybridization, and isolation of protein and RNA. Ovaries were also collected from midluteal phase and first-trimester pregnant cows. Luteal cells were prepared and sorted by centrifugal elutriation to obtain purified small (SLCs) and large luteal cells (LLCs). Real-time PCR and in situ hybridization showed that ATF3 mRNA increased within 1 hour of PGF treatment in vivo. Western blot and immunohistochemistry demonstrated that ATF3 protein was expressed in the nuclei of LLC within 1 hour and was maintained for at least 4 hours. PGF treatment in vitro increased ATF3 expression only in LLC, whereas TNF induced ATF3 in both SLCs and LLCs. PGF stimulated concentration- and time-dependent increases in ATF3 and phosphorylation of MAPKs in LLCs. Combinations of MAPK inhibitors suppressed ATF3 expression in LLCs. Adenoviral-mediated expression of ATF3 inhibited LH-stimulated cAMP response element reporter luciferase activity and progesterone production in LLCs and SLCs but did not alter cell viability or change the expression or activity of key regulators of progesterone synthesis. In conclusion, the action of PGF in LLCs is associated with the rapid activation of stress-activated protein kinases and the induction of ATF3, which may contribute to the reduction in steroid synthesis during luteal regression. ATF3 appears to affect gonadotropin-stimulated progesterone secretion at a step or steps downstream of PKA signaling and before cholesterol conversion to progesterone.
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Expression regulated by
LH, TNF
Comment
Prostaglandin F2α induces expression of activating transcription factor 3 (ATF3) and activates MAPK signaling in the rat corpus luteum. Guo N et al. (2015) The current study was conducted to evaluate the expression of ATF3, in association with the activation of mitogen-activated protein kinases (MAPK) during prostaglandin F2α analog (PGF)-induced luteal regression in rats. A sequential PMSG/hCG treatment paradigm was used to obtain a single, well-defined generation of corpora lutea (CL) in rats. Rats were treated with PGF for 0-4h on day 7 of pseudopregnancy. Results showed that serum progesterone (P4) concentrations declined in a time dependent manner. Western blot results revealed that ATF3 increased within 2h post-PGF injection. Phosphorylated ERK1/2 (p-ERK) and JNK (p-JNK) increased within 30min and then were gradually reduced in response to PGF. In contrast, the levels of phosphorylated p38 MAPK (p-p38) were not significantly altered. The immunostaining density for p-ERK decreased from the periphery to the center of the corpus luteum following treatment with PGF, while ATF3 was expressed uniformly in the nuclei of luteal steroidogenic cells. These results indicated that treatment with PGF in vivo could induce increases in MAPK phosphorylation, especially in p-ERK, which might be correlated with the increases in ATF3 expression and the decline in P4 concentrations. To our knowledge, this is the first study to provide evidence for temporal relationships between MAPK activation and ATF3 expression during PGF-induced luteal regression in the rat.//////////////////