ARAP2(ADP-ribosylation factor 6 GTPase-activating protein 2)是一种重要的细胞信号调节蛋白,属于Arf GAP家族,该家族成员通过调节ADP-ribosylation factor(Arf)GTPase活性,参与细胞内多种生物学过程,包括细胞骨架重构、细胞膜运输、脂质代谢、细胞增殖和凋亡等[7]。ARAP2作为Arf6的GAP,通过将Arf6·GTP转化为Arf6·GDP,抑制Rac1的激活,进而调控焦点黏附的形成和细胞迁移[3]。此外,ARAP2还通过调节鞘脂代谢,影响葡萄糖转运蛋白GLUT1的表达和定位,进而调控基础葡萄糖摄取[1]。
在癌症研究领域,ARAP2也受到了广泛关注。研究发现,环状RNA circ-ARAP2在食管鳞状细胞癌(ESCC)组织和细胞系中显著上调,并且通过调节miR-761/FOXM1轴,促进ESCC细胞的增殖、肿瘤生长和转移[2]。此外,ARAP2在前列腺癌肺转移中高表达,与免疫反应相关基因的表达上调有关,提示ARAP2可能参与前列腺癌的免疫逃逸[6]。
除了在癌症中的作用,ARAP2还与脂肪肝的发生发展密切相关。研究发现,ARAP2基因的变异与鹅的脂肪肝重量和生化指标相关,提示ARAP2可能参与鹅脂肪肝的形成[5]。此外,ARAP2还与人类唾液腺黏液表皮样癌的发生发展有关,其基因融合可能导致肿瘤的发生[4]。
在骨骼发育和软骨形成方面,ARAP2也发挥着重要作用。研究发现,ARAP2基因的表达与骨髓间充质干细胞(BMSC)的软骨分化相关,并且可能通过miRNA调控相关基因的表达,影响软骨的形成[8]。
综上所述,ARAP2作为一种重要的细胞信号调节蛋白,参与细胞内多种生物学过程,包括细胞骨架重构、细胞膜运输、脂质代谢、细胞增殖和凋亡等。ARAP2在癌症、脂肪肝、骨骼发育和软骨形成等方面发挥着重要作用,其功能机制和调控机制仍需进一步研究。
参考文献:
1. Chaudhari, Aditi, Håversen, Liliana, Mobini, Reza, Perkins, Rosie, Borén, Jan. 2016. ARAP2 promotes GLUT1-mediated basal glucose uptake through regulation of sphingolipid metabolism. In Biochimica et biophysica acta, 1861, 1643-1651. doi:10.1016/j.bbalip.2016.07.009. https://pubmed.ncbi.nlm.nih.gov/27476102/
2. Xu, Pei, Wang, Lei, Liu, Qingtao, Yang, Qi, Xiao, Haibo. 2022. The abnormal expression of circ-ARAP2 promotes ESCC progression through regulating miR-761/FOXM1 axis-mediated stemness and the endothelial-mesenchymal transition. In Journal of translational medicine, 20, 318. doi:10.1186/s12967-022-03507-3. https://pubmed.ncbi.nlm.nih.gov/35842667/
3. Chen, Pei-Wen, Jian, Xiaoying, Yoon, Hye-Young, Randazzo, Paul A. 2013. ARAP2 signals through Arf6 and Rac1 to control focal adhesion morphology. In The Journal of biological chemistry, 288, 5849-60. doi:10.1074/jbc.M112.415778. https://pubmed.ncbi.nlm.nih.gov/23295182/
4. Gu, Wenjin, Bhangale, Apurva, Heft Neal, Molly E, Mills, Ryan E, Brenner, J Chad. 2022. Analysis of Human Papilloma Virus Content and Integration in Mucoepidermoid Carcinoma. In Viruses, 14, . doi:10.3390/v14112353. https://pubmed.ncbi.nlm.nih.gov/36366450/
5. Yang, Yunzhou, Wang, Huiying, Li, Guangquan, Wang, Cui, He, Daqian. 2020. Exploring the genetic basis of fatty liver development in geese. In Scientific reports, 10, 14279. doi:10.1038/s41598-020-71210-8. https://pubmed.ncbi.nlm.nih.gov/32868783/
6. Saraji, Alireza, Wulf, Katharina, Stegmann-Frehse, Janine, Perner, Sven, Sailer, Verena Wilbeth. 2024. Comprehensive transcriptomic analysis of prostate cancer lung metastases. In PloS one, 19, e0306525. doi:10.1371/journal.pone.0306525. https://pubmed.ncbi.nlm.nih.gov/39146303/
7. Tanna, Christine E, Goss, Louisa B, Ludwig, Calvin G, Chen, Pei-Wen. 2019. Arf GAPs as Regulators of the Actin Cytoskeleton-An Update. In International journal of molecular sciences, 20, . doi:10.3390/ijms20020442. https://pubmed.ncbi.nlm.nih.gov/30669557/
8. Vail, Daniel J, Somoza, Rodrigo A, Caplan, Arnold I. 2021. MicroRNA Regulation of Bone Marrow Mesenchymal Stem Cell Chondrogenesis: Toward Articular Cartilage. In Tissue engineering. Part A, 28, 254-269. doi:10.1089/ten.TEA.2021.0112. https://pubmed.ncbi.nlm.nih.gov/34328786/