NCBI Summary:
This gene encodes a transcription factor that is a member of the leucine zipper family of DNA binding proteins. This protein binds to the cAMP-response element and regulates cell proliferation. The protein interacts with host cell factor C1, which also associates with the herpes simplex virus (HSV) protein VP16 that induces transcription of HSV immediate-early genes. This protein and VP16 both bind to the same site on host cell factor C1. It is thought that the interaction between this protein and host cell factor C1 plays a role in the establishment of latency during HSV infection. This protein also plays a role in leukocyte migration, tumor suppression, and endoplasmic reticulum stress-associated protein degradation. Additional transcript variants have been identified, but their biological validity has not been determined.[provided by RefSeq, Nov 2009]
General function
DNA binding, Transcription factor
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Cellular localization
Nuclear
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Ovarian function
Steroid metabolism, Early embryo development
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Knockdown of CREB3/Luman by shRNA in Mouse Granulosa Cells Results in Decreased Estradiol and Progesterone Synthesis and Promotes Cell Proliferation. Zhao F et al. (2016) Luman (also known as LZIP or CREB3) is a transcription factor and a member of the cAMP responsive element-binding (CREB) family proteins. Although Luman has been detected in apoptotic granulosa cells and disorganized atretic bodies, the physiological function of Luman in follicular development has not been reported. Our objective is to determine the role of Luman in folliculogenesis by knocking down Luman expression in mouse GCs (granulosa cells) using shRNA. Luman expression was successfully knocked down in mouse GCs at the mRNA and protein level, as confirmed by real-time quantitative PCR, western blot and immunofluorescence staining, respectively. Knockdown of Luman significantly decreased the concentrations of estradiol (E2) and progesterone (P4) in cell culture medium. Furthermore, Luman knockdown promoted cell proliferation but had no effect on cell apoptosis. To elucidate the regulatory mechanism underlying the effects of Luman knockdown on steroid synthesis and cell cycle, we measured the mRNA and protein expression levels of several related genes. The expression of Star, Cyp19a1, and Cyp1b1, which encode steroidogenic enzymes, was down-regulated, while that of Cyp11a1 and Runx2, which also encode steroidogenic enzymes, was up-regulated. The expression of the cell cycle factors Cyclin A1, Cyclin B1, Cyclin D2, and Cyclin E was significantly up-regulated. Among apoptosis-related genes, only Bcl-2 was down-regulated, while Caspase 3, Bax and p53 were not significantly affected, suggesting that Luman knockdown may regulate cell cycle activity and hormone secretion at the transcriptional and translational level in mouse GCs. The expression of two important genes associated with folliculogenesis in mouse GCs, Has2 and Ptgs2, were also significantly altered by Luman knockdown. In conclusion, the findings of this study indicate that Luman regulates mouse GCs modulation of steroid synthesis, cell cycle activity and other regulators of folliculogenesis.//////////////////
Expression regulated by
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Ovarian localization
Oocyte, Granulosa
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Expression and localization of Luman/CREB3 in mouse embryos during the pre-implantation period. Mahmoud TN et al. (2015) Luman/CREB3 is a transcription factor that is a member of the cAMP-response-element-binding protein family of basic region-leucine zipper transcription factors. This protein interacts with host cell factor 1, which also associates with the herpes simplex virus protein VP16 to induce the transcription of herpes simplex virus. Currently, the physiological function of Luman/CREB3 in reproductive processes remains unclear. In this study, quantitative real-time PCR and immunofluorescence assays were used to investigate the expression and localization of Luman in mouse oocytes as well as in early embryonic development. Luman protein was detected in the germinal vesicle and metaphase II stage oocytes, and was distributed in the cytoplasm, nucleus, and polar body of the oocyte stage. However, Luman protein and mRNA expression levels were significantly (P < 0.05) increased before activation of the zygotic genome, and expression levels peaked in 4-cell embryos. Expression levels were significantly (P < 0.05) decreased following the 8-cell stage throughout the blastocyst stage. The Luman protein was also distributed in the nucleus and cytoplasm in the early preimplantation embryo and showed enhanced nuclear staining starting from the 2-cell stage embryo up to the 8-cell stage embryo. The differences in the expression and localization of Luman in mouse oocytes and early embryo suggested that Luman plays an important role in oocyte maturation and early embryonic development processes.//////////////////