PPP2R5B,也称为蛋白磷酸酶2A(PP2A)的B56β亚基,是一种重要的蛋白磷酸酶调节亚基。PP2A是一种广泛存在的丝氨酸/苏氨酸蛋白磷酸酶,参与调节细胞内的多种生物学过程,包括细胞周期、信号传导、基因表达和代谢等。PPP2R5B作为PP2A的调节亚基,可以影响PP2A的活性和特异性,从而影响这些生物学过程。
PPP2R5B在多种疾病中发挥重要作用。例如,在多发性内分泌腺瘤病1型(MEN1)中,PPP2R5B被定位在染色体11q13的一个0.5-Mb区域内,但并没有发现与MEN1相关的突变[1]。在乳腺癌中,PPP2R5B与患者的生存率相关,并且与乳腺浸润的免疫细胞相关[2]。在胰岛素抵抗中,PPP2R5B的表达增加,并且可以负调节Akt蛋白的磷酸化,从而影响胰岛素信号传导和葡萄糖摄取[3]。在肝细胞癌(HCC)中,PPP2R5B的表达水平与患者的预后相关,并且与肿瘤微环境和免疫细胞浸润相关[4][5][6][7]。此外,PPP2R5B的表达也与细胞凋亡相关,并且可以影响HCC细胞的增殖和克隆能力[7]。
在人类过度生长综合征中,PPP2R5B基因突变可以导致过度生长和智力障碍[8]。此外,PPP2R5B基因突变还可以导致家族性乳腺癌,但并没有发现与家族性乳腺癌相关的突变[9]。
综上所述,PPP2R5B是一种重要的蛋白磷酸酶调节亚基,参与调节细胞内的多种生物学过程。PPP2R5B在多种疾病中发挥重要作用,包括MEN1、乳腺癌、胰岛素抵抗、HCC和过度生长综合征等。PPP2R5B的研究有助于深入理解PP2A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. Forbes, S A, Pannett, A A, Bassett, J H, Lips, C J, Kas, K. . Mapping of the gene encoding the B56 beta subunit of protein phosphatase 2A (PPP2R5B) to a 0.5-Mb region of chromosome 11q13 and its exclusion as a candidate gene for multiple endocrine neoplasia type 1 (MEN1). In Human genetics, 100, 481-5. doi:. https://pubmed.ncbi.nlm.nih.gov/9272177/
2. Ganaie, Ishfaq Ahmad, Malik, Md Zubbair, Mangangcha, Irengbam Rocky, Jain, Swatantra Kumar, Wajid, Saima. 2023. Identification of a survival associated gene trio in chemical induced breast cancer. In Biochimie, 208, 170-179. doi:10.1016/j.biochi.2023.01.003. https://pubmed.ncbi.nlm.nih.gov/36621662/
3. Beg, Muheeb, Srivastava, Ankita, Shankar, Kripa, Kumar, Durgesh, Gaikwad, Anil N. 2016. PPP2R5B, a regulatory subunit of PP2A, contributes to adipocyte insulin resistance. In Molecular and cellular endocrinology, 437, 97-107. doi:10.1016/j.mce.2016.08.016. https://pubmed.ncbi.nlm.nih.gov/27521959/
4. Lu, Yongpan, Wang, Sen, Chi, Tingting, Wang, Haizheng, Feng, Li. 2023. DNA damage repair-related gene signature for identifying the immune status and predicting the prognosis of hepatocellular carcinoma. In Scientific reports, 13, 18978. doi:10.1038/s41598-023-45999-z. https://pubmed.ncbi.nlm.nih.gov/37923899/
5. Hu, Yu, Deng, Jie, Tian, Ke, Zhang, Jiao-Jiao, Wang, Xian-Zhong. 2019. MiR-8-3p regulates hyperthermia-induced lactate secretion by targeting PPP2R5B in boar Sertoli cells. In Molecular reproduction and development, 86, 1720-1730. doi:10.1002/mrd.23265. https://pubmed.ncbi.nlm.nih.gov/31489750/
6. Liu, Peng, Wei, Jinhong, Mao, Feiyu, Qian, Jianjun, Yao, Jie. 2021. Establishment of a Prognostic Model for Hepatocellular Carcinoma Based on Endoplasmic Reticulum Stress-Related Gene Analysis. In Frontiers in oncology, 11, 641487. doi:10.3389/fonc.2021.641487. https://pubmed.ncbi.nlm.nih.gov/34094926/
7. He, Yuhong, Wu, Shihao, Chen, Lifan, Li, Mingyi, Liu, Bin. 2024. Constructing and validating pan-apoptosis-related features for predicting prognosis and immunotherapy response in hepatocellular carcinoma. In Biochemical and biophysical research communications, 734, 150633. doi:10.1016/j.bbrc.2024.150633. https://pubmed.ncbi.nlm.nih.gov/39243678/
8. Lemmens, I, Van de Ven, W J, Kas, K, Farnebo, F, Thakker, R V. . Identification of the multiple endocrine neoplasia type 1 (MEN1) gene. The European Consortium on MEN1. In Human molecular genetics, 6, 1177-83. doi:. https://pubmed.ncbi.nlm.nih.gov/9215690/
9. Loveday, Chey, Tatton-Brown, Katrina, Clarke, Matthew, van Montfort, Rob, Rahman, Nazneen. 2015. Mutations in the PP2A regulatory subunit B family genes PPP2R5B, PPP2R5C and PPP2R5D cause human overgrowth. In Human molecular genetics, 24, 4775-9. doi:10.1093/hmg/ddv182. https://pubmed.ncbi.nlm.nih.gov/25972378/