Naicker Danielle, Rhoda Cenza, Sunda Falone, Arowolo Afolake
Division of Medical Biochemistry, Department of Integrative Biomedical Sciences, University of Cape Town, Cape Town 7925, South Africa.
Hair and Skin Research Unit, Division of Dermatology, Department of Medicine, University of Cape Town, Cape Town 7925, South Africa.
Int J Mol Sci. 2024 Feb 29;25(5):2845. doi: 10.3390/ijms25052845.
Proteases are critical enzymes in cellular processes which regulate intricate events like cellular proliferation, differentiation and apoptosis. This review highlights the multifaceted roles of the serine proteases FAM111A and FAM111B, exploring their impact on cellular functions and diseases. FAM111A is implicated in DNA replication and replication fork protection, thereby maintaining genome integrity. Additionally, FAM111A functions as an antiviral factor against DNA and RNA viruses. Apart from being involved in DNA repair, FAM111B, a paralog of FAM111A, participates in cell cycle regulation and apoptosis. It influences the apoptotic pathway by upregulating anti-apoptotic proteins and modulating cell cycle-related proteins. Furthermore, FAM111B's association with nucleoporins suggests its involvement in nucleo-cytoplasmic trafficking and plays a role in maintaining normal telomere length. FAM111A and FAM111B also exhibit some interconnectedness and functional similarity despite their distinct roles in cellular processes and associated diseases resulting from their dysfunction. FAM111A and FAM111B dysregulation are linked to genetic disorders: Kenny-Caffey Syndrome type 2 and Gracile Bone Dysplasia for FAM111A and POIKTMP, respectively, and cancers. Therefore, the dysregulation of these proteases in diseases emphasizes their potential as diagnostic markers and therapeutic targets. Future research is essential to unravel the intricate mechanisms governing FAM111A and FAM111B and explore their therapeutic implications comprehensively.
蛋白酶是细胞过程中的关键酶,可调节细胞增殖、分化和凋亡等复杂事件。本综述重点介绍了丝氨酸蛋白酶FAM111A和FAM111B的多方面作用,探讨了它们对细胞功能和疾病的影响。FAM111A与DNA复制和复制叉保护有关,从而维持基因组完整性。此外,FAM111A作为一种针对DNA和RNA病毒的抗病毒因子发挥作用。除了参与DNA修复外,FAM111A的旁系同源物FAM111B还参与细胞周期调控和凋亡。它通过上调抗凋亡蛋白和调节细胞周期相关蛋白来影响凋亡途径。此外,FAM111B与核孔蛋白的关联表明其参与核质运输,并在维持正常端粒长度中发挥作用。尽管FAM111A和FAM111B在细胞过程及其功能障碍导致的相关疾病中发挥着不同作用,但它们也表现出一些相互联系和功能相似性。FAM111A和FAM111B的失调与遗传疾病有关:FAM111A与2型肯尼-卡菲综合征和纤细骨发育不良有关,FAM111B与POIKTMP有关,还与癌症有关。因此,这些蛋白酶在疾病中的失调强调了它们作为诊断标志物和治疗靶点的潜力。未来的研究对于阐明控制FAM111A和FAM111B的复杂机制并全面探索其治疗意义至关重要。