Cep78,也称为centrosomal protein 78 kDa,是一种定位于中心体的重要蛋白。中心体是细胞中负责微管组织、细胞分裂和纤毛形成的细胞器。Cep78在纤毛生成和纤毛长度控制中发挥关键作用,其突变会导致视网膜锥杆营养不良,并伴有听力损失[4]。此外,Cep78还与男性不育有关,其缺陷会导致精子数量减少、形态异常和运动能力丧失[1,3,7]。
研究发现,Cep78的功能与其与其他蛋白质的相互作用密切相关。例如,Cep78可以与E3泛素连接酶复合物EDD-DYRK2-DDB1VprBP相互作用,通过泛素化途径调节CP110的水平,进而影响中心体长度和纤毛组装[6,8]。此外,Cep78还可以与CEP350相互作用,促进CEP78在中心体的募集和稳定性,进而影响纤毛生成[6]。
Cep78的突变或缺失会导致多种疾病,包括男性不育、视网膜锥杆营养不良、Usher综合征和甲状腺癌。研究发现,Cep78的缺失会导致精子数量减少、形态异常和运动能力丧失,这是男性不育的重要原因之一[1,3,7]。此外,Cep78的突变或缺失还会导致视网膜锥杆营养不良,表现为视力下降、视野缩小和色觉异常[3,4]。Usher综合征是一种遗传性视网膜疾病,伴有听力损失。研究发现,Cep78的突变或缺失是Usher综合征的一个重要原因[4,5]。此外,Cep78的表达水平在甲状腺癌组织中显著降低,可以作为甲状腺癌和甲状腺结节的区分标志,并预测甲状腺癌患者发生颈部淋巴结转移的风险[2]。
综上所述,Cep78是一种重要的中心体蛋白,参与调控纤毛生成、纤毛长度控制和精子发生等过程。Cep78的突变或缺失会导致多种疾病,包括男性不育、视网膜锥杆营养不良、Usher综合征和甲状腺癌。Cep78的研究有助于深入理解中心体和纤毛的生物学功能,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. Zhang, Xueguang, Zheng, Rui, Liang, Chen, Yang, Yihong, Shen, Ying. 2022. Loss-of-function mutations in CEP78 cause male infertility in humans and mice. In Science advances, 8, eabn0968. doi:10.1126/sciadv.abn0968. https://pubmed.ncbi.nlm.nih.gov/36206347/
2. Hammad, Maha O, Elabbasy, Lamiaa M, Abd Elghaffar, Mahmoud A, Bazeed, Fagr B, Zahran, Mohammed A. 2019. Significance of CEP78 and WDR62 gene expressions in differentiated thyroid carcinoma: Possible predictors of lateral lymph node metastasis. In Asia-Pacific journal of clinical oncology, 15, e154-e161. doi:10.1111/ajco.13143. https://pubmed.ncbi.nlm.nih.gov/30884127/
3. Zhu, Tianyu, Zhang, Yuxin, Sheng, Xunlun, Guo, Xuejiang, Zhao, Chen. 2023. Absence of CEP78 causes photoreceptor and sperm flagella impairments in mice and a human individual. In eLife, 12, . doi:10.7554/eLife.76157. https://pubmed.ncbi.nlm.nih.gov/36756949/
4. Lähteenoja, Laura, Häkli, Sanna, Tuupanen, Sari, Rahikkala, Elisa, Falck, Aura. 2022. A novel frameshift variant in CEP78 associated with nonsyndromic retinitis pigmentosa, and a review of CEP78-related phenotypes. In Ophthalmic genetics, 43, 152-158. doi:10.1080/13816810.2022.2045511. https://pubmed.ncbi.nlm.nih.gov/35240912/
5. Fu, Qing, Xu, Mingchu, Chen, Xue, Sui, Ruifang, Chen, Rui. 2016. CEP78 is mutated in a distinct type of Usher syndrome. In Journal of medical genetics, 54, 190-195. doi:10.1136/jmedgenet-2016-104166. https://pubmed.ncbi.nlm.nih.gov/27627988/
6. Gonçalves, André Brás, Hasselbalch, Sarah Kirstine, Joensen, Beinta Biskopstø, Farinelli, Pietro, Pedersen, Lotte Bang. 2021. CEP78 functions downstream of CEP350 to control biogenesis of primary cilia by negatively regulating CP110 levels. In eLife, 10, . doi:10.7554/eLife.63731. https://pubmed.ncbi.nlm.nih.gov/34259627/
7. Liu, Min, Wen, Zongzhuang, Zhao, Dapeng, Gao, Jiangang, Yao, Zhiwei. 2025. Cep78 knockout causes sterility and oligoasthenoteratozoospermia in male mice. In Scientific reports, 15, 63. doi:10.1038/s41598-024-84006-x. https://pubmed.ncbi.nlm.nih.gov/39747485/
8. Hossain, Delowar, Javadi Esfehani, Yalda, Das, Arindam, Tsang, William Y. 2017. Cep78 controls centrosome homeostasis by inhibiting EDD-DYRK2-DDB1VprBP. In EMBO reports, 18, 632-644. doi:10.15252/embr.201642377. https://pubmed.ncbi.nlm.nih.gov/28242748/