Emerging roles of NudC family： from molecular regulation to clinical implications

Nuclear distribution gene C(Nud C) was first found in Aspergillus nidulans as an upstream regulator of Nud F, whose mammalian homolog is Lissencephaly 1(Lis1). Nud C is conserved from fungi to mammals. Vertebrate Nud C has three homologs: Nud C, Nud C-like protein(Nud CL), and Nud C-like protein 2(Nud CL2). All members of the Nud C 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 Nud C homologs were involved in cell cycle regulation by stabilizing the components of the LIS1/dynein complex. Additionally, Nud C plays important roles in cell migration, ciliogenesis, thrombopoiesis, and the inflammatory response. It has been reported that Nud CL is essential for the stability of the dynein intermediate chain and ciliogenesis via its interaction with the dynein 2 complex. Our data showed that Nud CL2 regulates the LIS1/dynein pathway by stabilizing LIS1 with Hsp90 chaperone. The fourth distantly related member of the Nud C 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 Nud C family and highlight its potential clinical relevance.

Nuclear distribution gene C （NudC） was first found in Aspergillus nidulans as an upstream regulator of NudF, whose mamma- lian homolog is Lissencephaly 1 （Lisl）. 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 LIS l/dynein complex. Additionally, NudC plays important roles in cell migration, ciliogenesis, thrombopoiesis, and the in- flammatory response. It has been reported that NudCL is essential for the stability of the dynein intermediate chain and cilio- genesis via its interaction with the dynein 2 complex. Our data showed that NudCL2 regulates the LISl/dynein pathway by stabilizing LIS 1 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 sig- naling pathway. In this review, we summarize our current knowledge of the NudC family and highlight its potential clinical relevance.