title: Emerging roles of MCPH1: expedition from primary microcephaly to cancer.
abstract: 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.
authors.affiliation: Department of Molecular Reproduction, Development and Genetics, Indian Institute of Science, Bangalore, Karnataka, India. Electronic address: thejaswinivenkatesh5@gmail.com.
authors.forename: Thejaswini
authors.initials: T
authors.lastname: Venkatesh
authors.affiliation: Centre for Biomedical Research, Vellore Institute of Technology University, Vellore, Tamil Nadu, India.
authors.forename: Padmanaban S
authors.initials: PS
authors.lastname: Suresh
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000502:physiology; D063646:Carcinogenesis / Q000378:metabolism; D059447:Cell Cycle Checkpoints / Q000502:physiology; D018797:Cell Cycle Proteins; D003598:Cytoskeletal Proteins; D004260:DNA Repair / Q000502:physiology; D006801:Humans; D008831:Microcephaly / Q000378:metabolism* / Q000473:pathology; D008938:Mitosis / Q000235:genetics; D023421:Models, Animal; D009369:Neoplasms / Q000378:metabolism* / Q000473:pathology; D009419:Nerve Tissue Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D010033:Otitis Media / Q000378:metabolism / Q000473:pathology; D019098:Telomerase / Q000378:metabolism; D016615:Telomere / Q000378:metabolism
chemical_list: D018797:Cell Cycle Proteins; D003598:Cytoskeletal Proteins; C460645:MCPH1 protein, human; D009419:Nerve Tissue Proteins; C509186:TERT protein, human; D019098:Telomerase
keywords: Apoptosis; Autosomal recessive primary microcephaly; BRIT1; Cancer; DNA repair; Glioblastoma; MCPH1; OSCC; Otitis media; miR-27a