NCBI Summary:
Interaction of Fas ligand (TNFSF6) with the FAS antigen (TNFRSF6) mediates programmed cell death, also called apoptosis, in a number of organ systems. The protein encoded by this gene binds to FAS antigen and can initiate apoptosis or enhance apoptosis initiated through FAS antigen. Initiation of apoptosis by the protein encoded by this gene requires a ubiquitin-like domain but not the FAS-binding domain. [provided by RefSeq, Jul 2008]
General function
Intracellular signaling cascade
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Cellular localization
Cytoplasmic
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Ovarian function
Oocyte maturation, Early embryo development
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Fas-associated protein factor 1 is involved in meiotic resumption in mouse oocytes. Peng H et al. (2018) Fas-associated protein factor 1 (FAF1) is a Fas-associated protein that functions in multiple cellular processes. Previous research showed that mutations in Faf1 led to the lethality of cleavage stage embryos in a mouse model. The aim of the present study was to analyze the expression pattern, localization, and function of FAF1 in meiotic resumption of mouse oocytes. FAF1 was exclusively expressed in oocytes at various follicular stages within the ovary and was predominantly localized in the cytoplasm of growing oocytes. Furthermore, Faf1 mRNA and protein were persistently present during oocyte maturation and Faf1 mRNA levels were similar in the germinal vesicle (GV), GV breakdown (GVBD), and metaphase II (MII) stages of oocytes. Moreover, knockdown of Faf1 in GV-stage oocytes led to a significantly decreased rate of GVBD. To our knowledge, these results provide the first evidence regarding a novel function of FAF1 in meiotic resumption in mouse oocytes.//////////////////
NLRP2 and FAF1 deficiency blocks early embryogenesis in the mouse. Peng H et al. (2017) Nlrp2 is a maternal effect gene specifically expressed by mouse ovaries; deletion of this gene from zygotes is known to result in early embryonic arrest. In the present study, we identified FAF1 protein as a specific binding partner of the NLRP2 protein in both mouse oocytes and preimplantation embryos. In addition to early embryos, both Faf1 mRNA and protein were detected in multiple tissues. NLRP2 and FAF1 proteins were co-localized to both the cytoplasm and nucleus during the development of oocytes and preimplantation embryos. Co-immunoprecipitation assays were used to confirm the specific interaction between NLRP2 and FAF1 proteins. Knockdown of the Nlrp2 or Faf1 gene in zygotes interfered with the formation of a NLRP2-FAF1 complex and led to developmental arrest during early embryogenesis. We therefore conclude that NLRP2 interacts with FAF1 under normal physiological conditions and that this interaction is probably essential for the successful development of cleavage-stage mouse embryos. Our data therefore indicated a potential role for NLRP2 in regulating early embryo development in the mouse.//////////////////
Expression regulated by
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Ovarian localization
Oocyte
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Fas-associated factor (FAF1) is required for the early cleavage-stages of mouse embryo. Adham IM et al. FAF1 was initially isolated as a Fas-associated factor and was subsequently found to interact with a subset of additional proteins that are involved in many cellular events including Fas-mediated apoptosis, heat shock signalling pathways and ubiquitin-dependent processes. Here, we describe that the 74-kDa FAF1 is ubiquitously expressed, while the expression of its posttranslational-processed 49-kDa isoform is restricted to post-meiotic male germ cells. In ovary, FAF1 protein is localized predominantly in the cytoplasm of oocytes in all follicle stages. To determine the function of FAF1 in vivo, we analysed a mouse mutant line in which a gene trap vector was inserted in the Faf1 locus. The mutation disrupts the Faf1 and leads to lethality of the Faf1(GT/GT) embryos near the 2-cell stage. Analysis of FAF1 expression revealed that the protein is present in early preimplantation stages, while embryonic expression of Faf1 mRNA becomes appreciable at 4-cell stage. These results indicate that the death of Faf1(GT/GT) at the 2-cell stage may coincide with the depletion of maternal FAF1 in these embryos. Thus, our results indicate that the FAF1 gene product is necessary for early embryonic development.