基因Siah2,也称为Seven in absentia homolog 2,是一种重要的RING E3泛素连接酶。Siah2在多种生物学过程中发挥重要作用,包括肿瘤发生、细胞分化和代谢等。Siah2能够与多种蛋白质相互作用,调节它们的泛素化降解,从而影响细胞内信号传导和基因表达。
在肿瘤发生中,Siah2表现出复杂的双重功能。一方面,Siah2可以促进肿瘤的发生和发展,如在前列腺癌、肺癌、胃癌和肝癌等多种人类恶性肿瘤中,Siah2的表达水平升高与肿瘤的发生和进展密切相关[1]。另一方面,Siah2也可以发挥肿瘤抑制功能,通过促进泛素化降解某些致癌蛋白,如HO-1,从而抑制肿瘤的生长[2]。此外,Siah2的表达和活性受到多种蛋白激酶的磷酸化调控,进一步增加了其功能的复杂性[1]。
在细胞分化过程中,Siah2也发挥着重要作用。例如,在脂肪生成过程中,Siah2能够与EBF1和ZFP521等蛋白质相互作用,调节ZFP521的蛋白水平,从而促进脂肪生成[3]。此外,Siah2还能够影响Wnt信号通路,进而影响脂肪细胞的分化和成熟[7]。
在代谢方面,Siah2也发挥着重要作用。例如,在肝脏中,Siah2能够与CBX2和EZH2等蛋白质相互作用,抑制Siah2的表达,进而促进糖酵解和肿瘤的生长[4]。此外,Siah2还能够影响铁代谢,从而影响铁死亡的进程[5,6]。
综上所述,Siah2是一种重要的RING E3泛素连接酶,参与调控多种生物学过程,包括肿瘤发生、细胞分化和代谢等。Siah2的功能受到多种因素的调控,表现出复杂的双重性。因此,深入研究Siah2的功能和调控机制,有助于揭示其生物学作用,为相关疾病的治疗和预防提供新的思路和策略。
参考文献:
1. Li, Kailang, Li, Jinyun, Ye, Meng, Jin, Xiaofeng. 2021. The role of Siah2 in tumorigenesis and cancer therapy. In Gene, 809, 146028. doi:10.1016/j.gene.2021.146028. https://pubmed.ncbi.nlm.nih.gov/34687788/
2. Chillappagari, Shashipavan, Belapurkar, Ratnal, Möller, Andreas, Rohrbach, Susanne, Schmitz, M Lienhard. 2020. SIAH2-mediated and organ-specific restriction of HO-1 expression by a dual mechanism. In Scientific reports, 10, 2268. doi:10.1038/s41598-020-59005-3. https://pubmed.ncbi.nlm.nih.gov/32042051/
3. Dang, Thanh N, Taylor, Jessica L, Kilroy, Gail, Burk, David H, Floyd, Z Elizabeth. 2020. SIAH2 is Expressed in Adipocyte Precursor Cells and Interacts with EBF1 and ZFP521 to Promote Adipogenesis. In Obesity (Silver Spring, Md.), 29, 98-107. doi:10.1002/oby.23013. https://pubmed.ncbi.nlm.nih.gov/33155406/
4. Xu, Zuoming, Wu, Yinghong, Yang, Meng, Wei, Huamei, Pu, Jian. 2023. CBX2-mediated suppression of SIAH2 triggers WNK1 accumulations to promote glycolysis in hepatocellular carcinoma. In Experimental cell research, 426, 113513. doi:10.1016/j.yexcr.2023.113513. https://pubmed.ncbi.nlm.nih.gov/36780970/
5. Shu, Fangzheng, Shi, Yuhua, Shan, Xiangxiang, Fan, Rengen, Xue, Wanjiang. . SIAH2-Mediated Degradation of ACSL4 Inhibits the Anti-Tumor Activity of CD8+ T Cells in Hepatocellular Carcinoma. In Critical reviews in eukaryotic gene expression, 34, 1-13. doi:10.1615/CritRevEukaryotGeneExpr.2024051981. https://pubmed.ncbi.nlm.nih.gov/38842200/
6. Yu, Yali, Dong, Guixiang, Niu, Yanli. 2024. Construction of ferroptosis-related gene signatures for identifying potential biomarkers and immune cell infiltration in osteoarthritis. In Artificial cells, nanomedicine, and biotechnology, 52, 449-461. doi:10.1080/21691401.2024.2402298. https://pubmed.ncbi.nlm.nih.gov/39258983/
7. Kilroy, Gail, Burk, David H, Floyd, Z Elizabeth. 2016. Siah2 Protein Mediates Early Events in Commitment to an Adipogenic Pathway. In The Journal of biological chemistry, 291, 27289-27297. doi:10.1074/jbc.M116.744672. https://pubmed.ncbi.nlm.nih.gov/27864366/