Abi2基因编码的是一种Abl相互作用蛋白(Abl-interactor),属于Abi家族的适配蛋白。Abi家族蛋白在细胞信号传导中扮演着重要角色,它们能够调节细胞骨架动力学,特别是在细胞粘附和迁移过程中。Abi2蛋白在多种细胞过程中发挥作用,包括细胞形态发生、迁移、粘附以及学习和记忆等认知功能[7]。
在植物中,Abi2是ABA信号传导途径中的一个关键调节因子。ABA是一种植物激素,对植物应对干旱、盐胁迫等非生物胁迫起着重要作用。Abi2属于2C型蛋白磷酸酶(PP2Cs)家族,其活性被ABA受体RCARs/PYR1/PYLs的激活所抑制[1,3]。当ABA与这些受体结合时,会导致PP2Cs如ABI1和ABI2的失活,从而启动SNF1型激酶的活性,调控ABA依赖的基因表达和离子通道,最终影响植物对胁迫的反应[1]。
Abi2在人类疾病中也扮演着重要的角色。在肝细胞癌(HCC)中,Abi2作为一个共激活因子,上调SLC17A9的表达,从而促进HCC的肿瘤发生和转移[2]。此外,Abi2在调节核蛋白方面也发挥着作用。研究表明,Abi2的过表达能够抑制三阴性乳腺癌(TNBC)细胞的增殖,通过调节PI3K/Akt信号通路影响核功能,如DNA修复和基因表达[4]。此外,Abi2还与血小板/淋巴细胞比率相关,在肾细胞癌(RCC)中,Abi2的表达水平与肿瘤分级和患者预后相关[6]。
在癌症研究中,Abi2的调节作用也被发现。例如,EB病毒编码的miR-BART13-3p能够下调Abi2的表达,从而通过上调c-JUN/SLUG信号通路促进鼻咽癌细胞的上皮-间质转化(EMT)和转移[8]。在乳腺癌中,PRR16蛋白通过与Abi2的相互作用,诱导上皮-间质转化,增强肿瘤细胞的迁移和侵袭[5]。
综上所述,Abi2是一种多功能蛋白,不仅在植物ABA信号传导中发挥关键作用,还在人类疾病中扮演重要角色。Abi2的调节作用涉及到多种生物学过程,包括细胞骨架动力学、细胞迁移、粘附、学习和记忆以及肿瘤发生和转移等。研究Abi2的功能和调节机制,有助于深入理解其生物学功能和疾病发生机制,为疾病的治疗和预防提供新的思路和策略。
参考文献:
1. Raghavendra, Agepati S, Gonugunta, Vijay K, Christmann, Alexander, Grill, Erwin. 2010. ABA perception and signalling. In Trends in plant science, 15, 395-401. doi:10.1016/j.tplants.2010.04.006. https://pubmed.ncbi.nlm.nih.gov/20493758/
2. Li, Huizi, Liu, Jin, Lai, Jie, Zhang, Tong, Gu, Qiuping. 2024. The HHEX-ABI2/SLC17A9 axis induces cancer stem cell-like properties and tumorigenesis in HCC. In Journal of translational medicine, 22, 537. doi:10.1186/s12967-024-05324-2. https://pubmed.ncbi.nlm.nih.gov/38844969/
3. Park, Sang-Youl, Fung, Pauline, Nishimura, Noriyuki, Volkman, Brian F, Cutler, Sean R. 2009. Abscisic acid inhibits type 2C protein phosphatases via the PYR/PYL family of START proteins. In Science (New York, N.Y.), 324, 1068-71. doi:10.1126/science.1173041. https://pubmed.ncbi.nlm.nih.gov/19407142/
4. Elavarasu, Santhosh Mudipalli, Vasudevan, Karthick, Sasikumar, K, Doss C, George Priya. 2025. The role of ABI2 in modulating nuclear proteins: Therapeutic implications for NUP54 and NUP153 in TNBC. In Advances in protein chemistry and structural biology, 143, 97-115. doi:10.1016/bs.apcsb.2024.09.011. https://pubmed.ncbi.nlm.nih.gov/39843146/
5. Kang, Gyeoung Jin, Park, Jung Ho, Kim, Hyun Ji, Rho, Seung Bae, Lee, Chang Hoon. 2022. PRR16/Largen Induces Epithelial-Mesenchymal Transition through the Interaction with ABI2 Leading to the Activation of ABL1 Kinase. In Biomolecules & therapeutics, 30, 340-347. doi:10.4062/biomolther.2022.066. https://pubmed.ncbi.nlm.nih.gov/35719027/
6. Ergun, Sercan, Gunes, Sezgin, Buyukalpelli, Recep, Aydin, Oguz. 2020. Association of Abl interactor 2, ABI2, with platelet/lymphocyte ratio in patients with renal cell carcinoma: A pilot study. In International journal of experimental pathology, 101, 87-95. doi:10.1111/iep.12349. https://pubmed.ncbi.nlm.nih.gov/32496656/
7. Grove, Matthew, Demyanenko, Galina, Echarri, Asier, Maness, Patricia F, Pendergast, Ann Marie. . ABI2-deficient mice exhibit defective cell migration, aberrant dendritic spine morphogenesis, and deficits in learning and memory. In Molecular and cellular biology, 24, 10905-22. doi:. https://pubmed.ncbi.nlm.nih.gov/15572692/
8. Huang, Jing, Qin, You, Yang, Chensu, Jin, Honglin, Yang, Kunyu. 2020. Downregulation of ABI2 expression by EBV-miR-BART13-3p induces epithelial-mesenchymal transition of nasopharyngeal carcinoma cells through upregulation of c-JUN/SLUG signaling. In Aging, 12, 340-358. doi:10.18632/aging.102618. https://pubmed.ncbi.nlm.nih.gov/31907338/