Ask about this productRelated genes to: RABGEF1 antibody
- Gene:
- RABGEF1 NIH gene
- Name:
- RAB guanine nucleotide exchange factor 1
- Previous symbol:
- -
- Synonyms:
- rabex-5, RABEX5
- Chromosome:
- 7q11.21
- Locus Type:
- gene with protein product
- Date approved:
- 2003-07-14
- Date modifiied:
- 2016-03-15
Related products to: RABGEF1 antibody
Related articles to: RABGEF1 antibody
- Neutrophils and macrophages are indispensable phagocytic immune cells, critically responsible for fish's ability to combat pathogens. Studies unveil that ATP7A is essential for copper trafficking to the lysosome in the cells, a process that is fundamental for their antibacterial functions in vitro. However, its antibacterial role in vivo and the underlying mechanisms have been insufficiently explored. In this study, we have demonstrated that atp7a mutant larvae are significantly more susceptible to Aeromonas hydrophila (AH) infection and possess fewer neutrophils and macrophages compared to their wild-type (WT) counterparts, and these mutants show a pronounced delay in the migration of the cells in response to infection. Atp7a deficiency leads to a marked downregulation of key phagosomal and lysosomal proteins, which impairs the formation of phagolysosomes and impairs lysosomal acidification and reactive oxygen species (ROS) elevation, then results in the ultimately impaired phagocytic activity and the attenuated release of phagolysosomal inflammatory and chemotactic signals such as il-1β/6/8, underscoring the impaired immune function of the mutants. Furthermore, Atp7a is shown to interact with proteins Lamp1 and Ctsb to facilitate copper trafficking and with Rabep1 and Rabgef1, to shield these proteins from degradation. Meanwhile, Atp7a-dependent copper trafficking is essential in Rabgef1 ubiquitination and the consequent activation of Rab5 and Rab7. These thereby enhance phagolysosomal activity and reinforce the immune response of neutrophils and macrophages against AH infection. In conclusion, this study compellingly establishes the pivotal role of Atp7a in sustaining the bactericidal capacities of immune cells in fish, while also illuminating the potential immune-related implications for individuals with ATP7A deficiency. - Source: PubMed
Jing YuanYuanShi JiaHaoXie ZhiJuanShen ZhengZhang JingjingWang FudiLi KuanyuSu JianguoLiu Jing-Xia - The spatiotemporal transition of small GTPase Rab5 to Rab7 is crucial for early-to-late endosome maturation, yet the precise mechanism governing Rab5-to-Rab7 switching remains elusive. USP8, a ubiquitin-specific protease, plays a prominent role in the endosomal sorting of a wide range of transmembrane receptors and is a promising target in cancer therapy. Here, we identified that USP8 is recruited to Rab5-positive carriers by Rabex5, a guanine nucleotide exchange factor (GEF) for Rab5. The recruitment of USP8 dissociates Rabex5 from early endosomes (EEs) and meanwhile promotes the recruitment of the Rab7 GEF SAND-1/Mon1. In USP8-deficient cells, the level of active Rab5 is increased, while the Rab7 signal is decreased. As a result, enlarged EEs with abundant intraluminal vesicles accumulate and digestive lysosomes are rudimentary. Together, our results reveal an important and unexpected role of a deubiquitinating enzyme in endosome maturation. - Source: PubMed
Publication date: 2024/11/22
Miao YueDu YongtaoWang BaoleiLiang JingjingLiang YuDang SongLiu JiahaoLi DongHe KangminDing Mei - Rabex-5 (also called RabGEF1), a protein originally characterized for its Rab5 GEF function, also has an A20-like E3 ubiquitin ligase domain. We and others reported that Rabex-5 E3 activity promotes Ras mono- and di-ubiquitination to inhibit Ras signaling in Drosophila and mammals. Subsequently, we reported that Rabex-5 inhibits Notch signaling in the Drosophila hematopoietic system. Here we report genetic interactions using Rabex-5 transgenes encoding domain-specific mutations that show that Rabex-5 requires an intact E3 domain to inhibit Notch signaling in the epithelial tissue of the developing wing. Surprisingly, we discovered that Rabex-5 with an impaired E3 domain but active Rab5 GEF domain suppresses Notch loss-of-function phenotypes and enhances both Notch duplication phenotypes and activated Ras phenotypes consistent with a model that the Rab5 GEF activity of Rabex-5 might positively regulate Ras and Notch. Positive and negative regulation of developmental signaling by its different catalytic domains could allow Rabex-5 to precisely coordinate developmental signaling to fine-tune patterning. Finally, we report that Rabex-5 also inhibits the overgrowth due to loss of PTEN or activation of PI3K but not activation of AKT. Inhibition of Ras, Notch, and PI3K signaling may explain why Rabex-5 is deleted in some cancers. Paradoxically, Rabex-5 is reported to be an oncogene in other cancers. We propose that Rabex-5 acts as a tumor suppressor via its E3 activity to inhibit Ras, Notch, and PI3K signaling and as an oncogene via its Rab5 GEF activity to enhance Ras and Notch signaling. - Source: PubMed
Publication date: 2024/10/28
Reimels Theresa ASteinberg MiaYan HuaShahar SivanRosenberg AshleyKalafsky KristinaLuf MaxKelly LindsayOctaviani StaciaPfleger Cathie M - Obesity shapes anti-tumor immunity through lipid metabolism; however, the mechanisms underlying how colorectal cancer (CRC) cells utilize lipids to suppress anti-tumor immunity remain unclear. Here, we show that tumor cell-intrinsic ATP6V0A1 drives exogenous cholesterol-induced immunosuppression in CRC. ATP6V0A1 facilitates cholesterol absorption in CRC cells through RAB guanine nucleotide exchange factor 1 (RABGEF1)-dependent endosome maturation, leading to cholesterol accumulation within the endoplasmic reticulum and elevated production of 24-hydroxycholesterol (24-OHC). ATP6V0A1-induced 24-OHC upregulates TGF-β1 by activating the liver X receptor (LXR) signaling. Subsequently, the release of TGF-β1 into the tumor microenvironment by CRC cells activates the SMAD3 pathway in memory CD8 T cells, ultimately suppressing their anti-tumor activities. Moreover, we identify daclatasvir, a clinically used anti-hepatitis C virus (HCV) drug, as an ATP6V0A1 inhibitor that can effectively enhance the memory CD8 T cell activity and suppress tumor growth in CRC. These findings shed light on the potential for ATP6V0A1-targeted immunotherapy in CRC. - Source: PubMed
Publication date: 2024/07/06
Huang Tu-XiongHuang Hui-SiDong Shao-WeiChen Jia-YanZhang BinLi Hua-HuiZhang Tian-TianXie QiangLong Qiao-YunYang YangHuang Lin-YuanZhao PanBi JiongLu Xi-FengPan FanZou ChangFu Li - Diabetic foot ulcers (DFU) is the most serious complication of diabetes mellitus, which has become a global health problem due to its high morbidity and disability rates and the poor efficacy of conventional treatments. Thus, it is urgent to identify novel molecular targets to improve the prognosis and reduce disability rate in DFU patients. - Source: PubMed
Publication date: 2024/06/11
Tan LonghaiQu JunjunWang Junxia