UBAP2L,即泛素关联蛋白2类似物,是一种在哺乳动物细胞中表达的蛋白质。它包含一个RGG结构域,这是一个富含精氨酸、甘氨酸和甘氨酸的序列,常出现在RNA结合蛋白中,并与其与RNA的结合活性相关[1]。UBAP2L已被证明可以与多种RNA相互作用,影响RNA的稳定性和翻译效率[1,2,3,4,5,6,7,8,9,10]。
UBAP2L与多种细胞生物学过程相关,包括细胞增殖、迁移、侵袭和凋亡。在多种类型的癌症中,UBAP2L的表达水平升高,并促进肿瘤的发生和进展[3,4,6,7,8,9]。例如,在非小细胞肺癌中,UBAP2L的扩增与患者的生存率降低相关[3]。此外,UBAP2L的过表达可以导致上皮-间质转化(EMT)样表型,这是肿瘤细胞侵袭和转移的重要过程[3]。
UBAP2L还可以与多种蛋白质相互作用,影响信号通路和基因表达。例如,UBAP2L可以与BMI1相互作用,影响造血干细胞(HSC)的活性[5]。BMI1是一种多梳抑制复合物(PcG)蛋白,对于HSC的自我更新和多能性维持至关重要[5]。此外,UBAP2L还可以激活Wnt/β-catenin信号通路,促进细胞增殖和肿瘤发生[4]。
UBAP2L的异常表达还与神经发育障碍(NDD)相关。UBAP2L的缺失可以导致小鼠的社交和认知障碍,并影响神经发生和应激颗粒的形成[2]。应激颗粒(SGs)是一种细胞质组装体,对多种应激反应至关重要[2]。
除了在肿瘤和神经发育中的作用外,UBAP2L还与纤维化相关。UBAP2L的沉默可以抑制成纤维细胞的增殖,并可能通过LIN28B增加UBAP2L mRNA的稳定性[9]。
总之,UBAP2L是一种在多种生物学过程中发挥重要作用的蛋白质。它在肿瘤发生、神经发育和纤维化中具有潜在的治疗价值。进一步研究UBAP2L的生物学功能和调控机制,将为开发新的治疗策略提供理论基础。
参考文献:
1. Luo, En-Ching, Nathanson, Jason L, Tan, Frederick E, Aigner, Stefan, Yeo, Gene W. 2020. Large-scale tethered function assays identify factors that regulate mRNA stability and translation. In Nature structural & molecular biology, 27, 989-1000. doi:10.1038/s41594-020-0477-6. https://pubmed.ncbi.nlm.nih.gov/32807991/
2. Jia, Xiangbin, Zhang, Shujie, Tan, Senwei, Shen, Yiping, Guo, Hui. 2022. De novo variants in genes regulating stress granule assembly associate with neurodevelopmental disorders. In Science advances, 8, eabo7112. doi:10.1126/sciadv.abo7112. https://pubmed.ncbi.nlm.nih.gov/35977029/
3. Aucagne, Romain, Girard, Simon, Mayotte, Nadine, Chagraoui, Jalila, Sauvageau, Guy. 2017. UBAP2L is amplified in a large subset of human lung adenocarcinoma and is critical for epithelial lung cell identity and tumor metastasis. In FASEB journal : official publication of the Federation of American Societies for Experimental Biology, 31, 5012-5018. doi:10.1096/fj.201601219RRR. https://pubmed.ncbi.nlm.nih.gov/28754713/
4. Lin, Sihan, Yan, Zhiyong, Tang, Qiaofei, Zhang, Shuang. . Ubiquitin-associated protein 2 like (UBAP2L) enhances growth and metastasis of gastric cancer cells. In Bioengineered, 12, 10232-10245. doi:10.1080/21655979.2021.1982308. https://pubmed.ncbi.nlm.nih.gov/34823423/
5. Bordeleau, Marie-Eve, Aucagne, Romain, Chagraoui, Jalila, Meloche, Sylvain, Sauvageau, Guy. 2014. UBAP2L is a novel BMI1-interacting protein essential for hematopoietic stem cell activity. In Blood, 124, 2362-9. doi:10.1182/blood-2014-01-548651. https://pubmed.ncbi.nlm.nih.gov/25185265/
6. Li, Qian, Wang, Wei, Hu, Yu-Chen, Yin, Tian-Tian, He, Jie. 2018. Knockdown of Ubiquitin Associated Protein 2-Like (UBAP2L) Inhibits Growth and Metastasis of Hepatocellular Carcinoma. In Medical science monitor : international medical journal of experimental and clinical research, 24, 7109-7118. doi:10.12659/MSM.912861. https://pubmed.ncbi.nlm.nih.gov/30291221/
7. Ye, Tao, Xu, Jing, Du, Ling, Liang, Yiming, Xia, Jinglin. 2017. Downregulation of UBAP2L Inhibits the Epithelial-Mesenchymal Transition via SNAIL1 Regulation in Hepatocellular Carcinoma Cells. In Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology, 41, 1584-1595. doi:10.1159/000470824. https://pubmed.ncbi.nlm.nih.gov/28334716/
8. Guan, Wei, Yang, Nan, Zuo, Xianglin, Xu, Zekuan, Sun, Yujie. 2021. Heritable Variants in the Chromosome 1q22 Locus Increase Gastric Cancer Risk via Altered Chromatin Looping and Increased UBAP2L Expression. In Molecular cancer research : MCR, 19, 1992-2002. doi:10.1158/1541-7786.MCR-21-0001. https://pubmed.ncbi.nlm.nih.gov/34535561/
9. Huang, Rui, Yang, Qixia, Wang, Tiantian. 2021. Norcantharidin-blocked ANXA2P2 inhibits fibroblast proliferation by increasing UBAP2L mRNA stability through LIN28B. In Life sciences, 279, 119645. doi:10.1016/j.lfs.2021.119645. https://pubmed.ncbi.nlm.nih.gov/34043991/
10. Li, Dong, Huang, Yiran. 2014. Knockdown of ubiquitin associated protein 2-like inhibits the growth and migration of prostate cancer cells. In Oncology reports, 32, 1578-84. doi:10.3892/or.2014.3360. https://pubmed.ncbi.nlm.nih.gov/25069639/