YBX2,也称为Y-box结合蛋白2,是一种在多种生物学过程中发挥重要作用的RNA结合蛋白。YBX2属于YBX家族,是一类在细胞中广泛表达的蛋白质,具有高度保守的冷休克结构域,能够与DNA和RNA分子相互作用,参与调控基因表达和RNA代谢过程。
YBX2在多种癌症的发生和发展中发挥作用。例如,在子宫内膜癌细胞中,YBX2能够通过与其m6A阅读蛋白YTHDF2相互作用,调节mRNA的稳定性,从而影响基因表达和细胞功能[1]。此外,YBX2还与癌症睾丸抗原CT45协同作用,促进癌症干细胞的特性、化疗耐药性和高度恶性[5]。在泛癌症分析中,YBX2被发现是一个潜在的生物标志物,与多种恶性通路和免疫相关特征相关[2]。
YBX2在生殖过程中也发挥重要作用。研究发现,YBX2基因的突变与男性因子不育有关,可能通过影响精子的DNA凝聚和表型导致不育[3,9]。此外,YBX2在精子的形成过程中也发挥重要作用,通过与mRNA相互作用,抑制翻译和阻断翻译依赖的mRNA降解,从而实现mRNA在精子中的储存[6,8]。
除了在癌症和生殖过程中的作用外,YBX2还参与其他生物学过程。例如,YBX2在棕色脂肪细胞中能够被磷酸化修饰,稳定其蛋白质水平,促进糖酵解和生热[4]。此外,YBX2还与Ribc2相互作用,在多毛细胞的纤毛摆动中发挥重要作用[7]。
综上所述,YBX2是一种在多种生物学过程中发挥重要作用的RNA结合蛋白,参与调控基因表达、RNA代谢、癌症发生、生殖过程和其他生物学过程。YBX2的研究有助于深入理解RNA结合蛋白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. Cai, Ying, Li, Na, Li, Huaibiao. 2023. YBX2 modulates mRNA stability via interaction with YTHDF2 in endometrial cancer cells. In Experimental cell research, 427, 113586. doi:10.1016/j.yexcr.2023.113586. https://pubmed.ncbi.nlm.nih.gov/37030331/
2. Yuan, Ze, Li, Binbin, Liao, Wenmin, Hu, Dandan, Chen, Aiqin. 2024. Comprehensive pan-cancer analysis of YBX family reveals YBX2 as a potential biomarker in liver cancer. In Frontiers in immunology, 15, 1382520. doi:10.3389/fimmu.2024.1382520. https://pubmed.ncbi.nlm.nih.gov/38698857/
3. Hammoud, Sue, Emery, Benjamin R, Dunn, Diane, Weiss, Robert B, Carrell, Douglas T. 2008. Sequence alterations in the YBX2 gene are associated with male factor infertility. In Fertility and sterility, 91, 1090-5. doi:10.1016/j.fertnstert.2008.01.009. https://pubmed.ncbi.nlm.nih.gov/18339382/
4. Zhao, Qingwen, Yu, Chao, Xu, Xiaoxuan, Gao, Yue, Pan, Dongning. 2023. Phosphorylated YBX2 is stabilized to promote glycolysis in brown adipocytes. In iScience, 26, 108091. doi:10.1016/j.isci.2023.108091. https://pubmed.ncbi.nlm.nih.gov/37860762/
5. Suzuki, Izumi, Yoshida, Sachiko, Tabu, Kouichi, Takeda, Satoru, Kato, Kiyoko. 2021. YBX2 and cancer testis antigen 45 contribute to stemness, chemoresistance and a high degree of malignancy in human endometrial cancer. In Scientific reports, 11, 4220. doi:10.1038/s41598-021-83200-5. https://pubmed.ncbi.nlm.nih.gov/33602962/
6. Kleene, Kenneth C. 2016. Position-dependent interactions of Y-box protein 2 (YBX2) with mRNA enable mRNA storage in round spermatids by repressing mRNA translation and blocking translation-dependent mRNA decay. In Molecular reproduction and development, 83, 190-207. doi:10.1002/mrd.22616. https://pubmed.ncbi.nlm.nih.gov/26773323/
7. Wang, Xiuzhi, Wang, Mengke, Dai, Xinyuan, Huang, Ying, Yang, Yun-Gui. 2021. RNA 5-methylcytosine regulates YBX2-dependent liquid-liquid phase separation. In Fundamental research, 2, 48-55. doi:10.1016/j.fmre.2021.10.008. https://pubmed.ncbi.nlm.nih.gov/38933916/
8. Kwon, Keun Yeong, Jeong, Hyeongsun, Jang, Dong Gil, Kwon, Taejoon, Park, Tae Joo. 2022. Ckb and Ybx2 interact with Ribc2 and are necessary for the ciliary beating of multi-cilia. In Genes & genomics, 45, 157-167. doi:10.1007/s13258-022-01350-w. https://pubmed.ncbi.nlm.nih.gov/36508087/
9. Aydos, Oya Sena E, Hekmatshoar, Yalda, Altınok, Buket, Sunguroğlu, Asuman, Aydos, Kaan. 2017. Genetic Polymorphisms in PRM1, PRM2, and YBX2 Genes are Associated with Male Factor Infertility. In Genetic testing and molecular biomarkers, 22, 55-61. doi:10.1089/gtmb.2017.0040. https://pubmed.ncbi.nlm.nih.gov/29227750/