OTUB2,也称为OTU域包含的泛素醛结合蛋白2,是一种重要的去泛素化酶(DUBs)。去泛素化酶是一类能够特异性切割泛素蛋白与底物蛋白之间连接的酶,参与调节细胞内多种蛋白质的降解和功能。泛素化是一种重要的蛋白质翻译后修饰,参与调节细胞内的许多生物学过程,包括细胞周期、DNA损伤修复、信号传导、细胞凋亡和蛋白质稳态等。
OTUB2在多种癌症中发挥重要作用,包括结直肠癌、卵巢癌、肝癌、胃癌、子宫内膜癌、非小细胞肺癌、食管鳞状细胞癌和结肠癌。在结直肠癌中,OTUB2通过促进PKM2活性和糖酵解来加剧肿瘤的进展[1]。在卵巢癌中,OTUB2的沉默通过线粒体代谢重编程促进肿瘤发生和化疗耐药性[2]。在肝癌中,OTUB2通过去泛素化PJA1来促进肿瘤的恶性增殖和转移[3]。在胃癌中,OTUB2通过促进KDM1A介导的干细胞样特性来促进肿瘤的发生[4]。在子宫内膜癌中,OTUB2通过调节PKM2介导的PI3K/AKT信号通路来促进肿瘤的进展[5]。在非小细胞肺癌中,OTUB2通过稳定U2AF2来促进Warburg效应和肿瘤的发生[6]。在食管鳞状细胞癌中,OTUB2通过circRNA6448-14/miR-455-3p/OTUB2轴来刺激糖酵解和干细胞特性[7]。在结肠癌中,OTUB2通过调节GINS1表达来调节干细胞特性、化疗耐药性和上皮-间质转化(EMT)[8]。
OTUB2在肝脏癌中也发挥重要作用,通过抑制NF-κB信号通路来抑制肿瘤细胞的生长[9]。此外,OTUB2还与一些神经退行性疾病相关,如肌萎缩侧索硬化症(ALS),在ALS中,OTUB2的表达上调[10]。
综上所述,OTUB2是一种重要的去泛素化酶,参与调节细胞内多种生物学过程,包括代谢、肿瘤发生、细胞凋亡和信号传导等。OTUB2在多种癌症中发挥重要作用,可能成为癌症治疗的新靶点。同时,OTUB2的研究有助于深入理解去泛素化酶的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. Yu, Shuyu, Zang, Weicheng, Qiu, Yuchong, Liao, Liming, Zheng, Xiaofeng. 2021. Deubiquitinase OTUB2 exacerbates the progression of colorectal cancer by promoting PKM2 activity and glycolysis. In Oncogene, 41, 46-56. doi:10.1038/s41388-021-02071-2. https://pubmed.ncbi.nlm.nih.gov/34671086/
2. Nan, Yabing, Wu, Xiaowei, Luo, Qingyu, Zhang, Lingqiang, Liu, Zhihua. 2024. OTUB2 silencing promotes ovarian cancer via mitochondrial metabolic reprogramming and can be synthetically targeted by CA9 inhibition. In Proceedings of the National Academy of Sciences of the United States of America, 121, e2315348121. doi:10.1073/pnas.2315348121. https://pubmed.ncbi.nlm.nih.gov/38701117/
3. Hu, Gang, Yang, Jianwu, Zhang, Hongwen, Huang, Zhen, Yang, Heming. 2022. OTUB2 Promotes Proliferation and Migration of Hepatocellular Carcinoma Cells by PJA1 Deubiquitylation. In Cellular and molecular bioengineering, 15, 281-292. doi:10.1007/s12195-022-00720-4. https://pubmed.ncbi.nlm.nih.gov/35611163/
4. Liu, Guangming, Guo, Wei, Qin, Junjie, Lin, Zhiliang. 2021. OTUB2 Facilitates Tumorigenesis of Gastric Cancer Through Promoting KDM1A-Mediated Stem Cell-Like Properties. In Frontiers in oncology, 11, 711735. doi:10.3389/fonc.2021.711735. https://pubmed.ncbi.nlm.nih.gov/34646768/
5. Zhang, Qian, Zhang, Jing, Yao, Anmei, Tao, Kai, Yang, Xuemei. 2022. OTUB2 promotes the progression of endometrial cancer by regulating the PKM2-mediated PI3K/AKT signaling pathway. In Cell biology international, 47, 428-438. doi:10.1002/cbin.11950. https://pubmed.ncbi.nlm.nih.gov/36316812/
6. Li, Jing, Cheng, Dongdong, Zhu, Miaoxin, Yan, Mingxia, Yao, Ming. 2019. OTUB2 stabilizes U2AF2 to promote the Warburg effect and tumorigenesis via the AKT/mTOR signaling pathway in non-small cell lung cancer. In Theranostics, 9, 179-195. doi:10.7150/thno.29545. https://pubmed.ncbi.nlm.nih.gov/30662561/
7. Gu, Zhen-Lin, Huang, Jing, Zhen, Lin-Lin. 2020. Knockdown of otubain 2 inhibits liver cancer cell growth by suppressing NF-κB signaling. In The Kaohsiung journal of medical sciences, 36, 399-404. doi:10.1002/kjm2.12187. https://pubmed.ncbi.nlm.nih.gov/32003539/
8. Zhang, Yaowen, Zhang, Heming, Wang, Chenyu, Ren, Runchuan, Zhou, Fuyou. 2024. circRNA6448-14/miR-455-3p/OTUB2 axis stimulates glycolysis and stemness of esophageal squamous cell carcinoma. In Aging, 16, 9485-9497. doi:10.18632/aging.205879. https://pubmed.ncbi.nlm.nih.gov/38819228/
9. Zhu, Wenjie, Wu, Changlei, Liu, Zitao, Zhao, ShiMin, Huang, Jun. 2024. OTU deubiquitinase, ubiquitin aldehyde binding 2 (OTUB2) modulates the stemness feature, chemoresistance, and epithelial-mesenchymal transition of colon cancer via regulating GINS complex subunit 1 (GINS1) expression. In Cell communication and signaling : CCS, 22, 420. doi:10.1186/s12964-024-01789-2. https://pubmed.ncbi.nlm.nih.gov/39210373/
10. Kudo, Lili C, Parfenova, Liubov, Vi, Nancy, Wiedau-Pazos, Martina, Karsten, Stanislav L. 2010. Integrative gene-tissue microarray-based approach for identification of human disease biomarkers: application to amyotrophic lateral sclerosis. In Human molecular genetics, 19, 3233-53. doi:10.1093/hmg/ddq232. https://pubmed.ncbi.nlm.nih.gov/20530642/