title: Emerging roles of NudC family: from molecular regulation to clinical implications.
abstract: Nuclear distribution gene C (NudC) was first found in Aspergillus nidulans as an upstream regulator of NudF, whose mammalian homolog is Lissencephaly 1 (Lis1). NudC is conserved from fungi to mammals. Vertebrate NudC has three homologs: NudC, NudC-like protein (NudCL), and NudC-like protein 2 (NudCL2). All members of the NudC family share a conserved p23 domain, which possesses chaperone activity both in conjunction with and independently of heat shock protein 90 (Hsp90). Our group and the others found that NudC homologs were involved in cell cycle regulation by stabilizing the components of the LIS1/dynein complex. Additionally, NudC plays important roles in cell migration, ciliogenesis, thrombopoiesis, and the inflammatory response. It has been reported that NudCL is essential for the stability of the dynein intermediate chain and ciliogenesis via its interaction with the dynein 2 complex. Our data showed that NudCL2 regulates the LIS1/dynein pathway by stabilizing LIS1 with Hsp90 chaperone. The fourth distantly related member of the NudC family, CML66, a tumor-associated antigen in human leukemia, contains a p23 domain and appears to promote oncogenesis by regulating the IGF-1R-MAPK signaling pathway. In this review, we summarize our current knowledge of the NudC family and highlight its potential clinical relevance.
authors.affiliation: Department of Cell Biology and Program in Molecular Cell Biology, Zhejiang University School of Medicine, Hangzhou, 310058, China.
authors.forename: Qiqin
authors.initials: Q
authors.lastname: Fu
authors.affiliation: Department of Cell Biology and Program in Molecular Cell Biology, Zhejiang University School of Medicine, Hangzhou, 310058, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Wang
authors.affiliation: Department of Cell Biology and Program in Molecular Cell Biology, Zhejiang University School of Medicine, Hangzhou, 310058, China. tzhou@zju.edu.cn.|Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Hangzhou, 310003, China. tzhou@zju.edu.cn.
authors.forename: Tianhua
authors.initials: T
authors.lastname: Zhou
authors.affiliation: Department of Cell Biology and Program in Molecular Cell Biology, Zhejiang University School of Medicine, Hangzhou, 310058, China. yhyang@zju.edu.cn.|Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Hangzhou, 310003, China. yhyang@zju.edu.cn.
authors.forename: Yuehong
authors.initials: Y
authors.lastname: Yang
mesh_terms: D000818:Animals; D018797:Cell Cycle Proteins / Q000502:physiology*; D006801:Humans; D018832:Molecular Chaperones / Q000502:physiology; D009687:Nuclear Proteins / Q000502:physiology*
chemical_list: D018797:Cell Cycle Proteins; D018832:Molecular Chaperones; D009687:Nuclear Proteins
keywords: Lissencephaly 1; cell cycle; ciliogenesis; dynein; heat shock protein 90; nuclear distribution gene C; p23