Department of Molecular Reproduction, Development and Genetics, Indian Institute of Science, Bangalore, Karnataka, India.
Centre for Biomedical Research, Vellore Institute of Technology University, Vellore, Tamil Nadu, India.
Eur J Cell Biol. 2014 Mar;93(3):98-105. doi: 10.1016/j.ejcb.2014.01.005. Epub 2014 Jan 29.
Genetic mutations in microcephalin1 (MCPH1) cause primary autosomal recessive microcephaly which is characterized by a marked reduction in brain size. MCPH1 encodes a centrosomal protein with three BRCT (BRCA1 C-terminal) domains. Also, it is a key regulator of DNA repair pathway and cell cycle checkpoints. Interestingly, in the past few years, many research studies have explored the role of MCPH1, a neurodevelopmental gene in several cancers and its tumor suppressor functions have been elucidated. Given the diverse new emerging roles, it becomes critical to review and summarize the multiple roles of MCPH1 that is currently lacking in the literature. In this review after systematic analysis of literature, we summarise the multiple functional roles of MCPH1 in centrosomal, DNA repair and apoptotic pathways. Additionally, we discuss the considerable efforts taken to understand the implications of MCPH1 in diseases such as primary microcephaly and its other emerging association with cancer and otitis media. The promising view is that MCPH1 has distinct roles and its clinical associations in various diseases makes it an attractive therapeutic target.
微脑畸形蛋白 1（MCPH1）基因突变导致原发性常染色体隐性小头畸形，其特征是大脑体积明显缩小。MCPH1 编码一种中心体蛋白，具有三个 BRCT（BRCA1 C 端）结构域。此外，它还是 DNA 修复途径和细胞周期检查点的关键调节因子。有趣的是，在过去的几年中，许多研究已经探索了 MCPH1（一种神经发育基因）在多种癌症中的作用，其肿瘤抑制功能已被阐明。鉴于新出现的多种作用，现在迫切需要对 MCPH1 的多种作用进行综述和总结，而这在文献中目前还缺乏。在对文献进行系统分析后，我们在这篇综述中总结了 MCPH1 在中心体、DNA 修复和细胞凋亡途径中的多种功能作用。此外，我们还讨论了为了解 MCPH1 在原发性小头畸形等疾病中的意义以及它与癌症和中耳炎等其他新兴关联而付出的巨大努力。有希望的观点是，MCPH1 具有不同的作用，其在各种疾病中的临床关联使其成为一个有吸引力的治疗靶点。
