Zdhhc9(Zinc finger DHHC-type containing 9)是一种X连锁基因,编码一种包含锌指DHHC结构域的蛋白。DHHC结构域是一种保守的结构,与蛋白质的S-棕榈酰化修饰有关。棕榈酰化是一种可逆的翻译后修饰,通过将棕榈酸(一种长链脂肪酸)共价连接到蛋白质的半胱氨酸残基上,影响蛋白质的膜定位、稳定性、活性及其与其他蛋白的相互作用。Zdhhc9在多种生物学过程中发挥重要作用,包括神经系统发育、肿瘤发生和免疫反应等。
参考文献1报道了Zdhhc9在脑胶质瘤中的作用。研究发现,Zdhhc9通过S-棕榈酰化葡萄糖转运蛋白GLUT1,促进GLUT1在质膜上的定位,从而增加葡萄糖的摄取,促进脑胶质瘤细胞的糖酵解和肿瘤发生[1]。参考文献2则揭示了Zdhhc9在膀胱癌中的作用。研究发现,Zdhhc9通过S-棕榈酰化Bip/GRP78蛋白,抑制未折叠蛋白反应(UPR),从而促进膀胱癌的进展[2]。
参考文献3和4研究了Zdhhc9在神经系统发育中的作用。研究发现,Zdhhc9的缺失导致神经元树突生长受损和抑制性突触形成减少,进而导致X连锁智力障碍(XLID)和癫痫的发生[3,4]。参考文献5和6则揭示了Zdhhc9在肿瘤免疫中的作用。研究发现,Zdhhc9通过S-棕榈酰化cGAS蛋白,促进cGAS的二聚化和激活,从而增强抗肿瘤免疫反应[5]。参考文献7和8则进一步研究了Zdhhc9在肺癌和结直肠癌中的作用。研究发现,Zdhhc9通过S-棕榈酰化PD-L1蛋白,影响PD-L1的稳定性,从而影响肿瘤细胞的免疫逃逸[6,7]。
参考文献9和10则进一步研究了Zdhhc9在乳腺癌和结肠癌中的作用。研究发现,Zdhhc9的表达与乳腺癌和结肠癌的预后相关,抑制Zdhhc9的表达可以增强肿瘤细胞的免疫反应,从而抑制肿瘤的生长[8,9]。
综上所述,Zdhhc9是一种重要的棕榈酰转移酶,通过S-棕榈酰化修饰多种蛋白质,影响神经系统的发育、肿瘤的发生和发展以及免疫反应。Zdhhc9的研究有助于深入理解棕榈酰化修饰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. Zhang, Zhenxing, Li, Xin, Yang, Fan, Zeng, Yi-Xin, Li, Xinjian. 2021. DHHC9-mediated GLUT1 S-palmitoylation promotes glioblastoma glycolysis and tumorigenesis. In Nature communications, 12, 5872. doi:10.1038/s41467-021-26180-4. https://pubmed.ncbi.nlm.nih.gov/34620861/
2. Li, Weiquan, Liu, Jingchong, Yu, Tiexi, Yang, Hongmei, Zhang, Xiaoping. 2024. ZDHHC9-mediated Bip/GRP78 S-palmitoylation inhibits unfolded protein response and promotes bladder cancer progression. In Cancer letters, 598, 217118. doi:10.1016/j.canlet.2024.217118. https://pubmed.ncbi.nlm.nih.gov/39002690/
3. Shimell, Jordan J, Shah, Bhavin S, Cain, Stuart M, Snutch, Terrance P, Bamji, Shernaz X. . The X-Linked Intellectual Disability Gene Zdhhc9 Is Essential for Dendrite Outgrowth and Inhibitory Synapse Formation. In Cell reports, 29, 2422-2437.e8. doi:10.1016/j.celrep.2019.10.065. https://pubmed.ncbi.nlm.nih.gov/31747610/
4. Kouskou, Marianna, Thomson, David M, Brett, Ros R, Pratt, Judith A, Chamberlain, Luke H. 2018. Disruption of the Zdhhc9 intellectual disability gene leads to behavioural abnormalities in a mouse model. In Experimental neurology, 308, 35-46. doi:10.1016/j.expneurol.2018.06.014. https://pubmed.ncbi.nlm.nih.gov/29944857/
5. Fan, Yizeng, Gao, Yang, Nie, Li, Wei, Wenyi, Li, Lei. . Targeting LYPLAL1-mediated cGAS depalmitoylation enhances the response to anti-tumor immunotherapy. In Molecular cell, 83, 3520-3532.e7. doi:10.1016/j.molcel.2023.09.007. https://pubmed.ncbi.nlm.nih.gov/37802025/
6. Li, Zhe, Jiang, Da, Liu, Fengling, Li, Ying. 2023. Involvement of ZDHHC9 in lung adenocarcinoma: regulation of PD-L1 stability via palmitoylation. In In vitro cellular & developmental biology. Animal, 59, 193-203. doi:10.1007/s11626-023-00755-5. https://pubmed.ncbi.nlm.nih.gov/37002491/
7. Schirwani, Schaida, Wakeling, Emma, Smith, Kath, Balasubramanian, Meena. . Expanding the molecular basis and phenotypic spectrum of ZDHHC9-associated X-linked intellectual disability. In American journal of medical genetics. Part A, 176, 1238-1244. doi:10.1002/ajmg.a.38683. https://pubmed.ncbi.nlm.nih.gov/29681091/
8. Chong, Xiaodan, Zhu, Lingxi, Yu, Dong, Chen, Haitao, An, Huazhang. 2022. ZDHHC9 promotes colon tumor growth by inhibiting effector T cells. In Oncology letters, 25, 5. doi:10.3892/ol.2022.13591. https://pubmed.ncbi.nlm.nih.gov/36419754/
9. Mitchell, David A, Hamel, Laura D, Reddy, Krishna D, Sanchez, Phillip R, Deschenes, Robert J. 2014. Mutations in the X-linked intellectual disability gene, zDHHC9, alter autopalmitoylation activity by distinct mechanisms. In The Journal of biological chemistry, 289, 18582-92. doi:10.1074/jbc.M114.567420. https://pubmed.ncbi.nlm.nih.gov/24811172/