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.
Highlights
Cytoplasmic dynein is a well-known minus-end-directed microtubule motor present in most eukaryotic cells (Cianfrocco et al, 2015; Chen et al, 2014; Can et al, 2014)
Our data showed that NudC-like protein 2 (NudCL2) regulates the LIS1/dynein pathway by stabilizing LIS1 with heat shock protein 90 (Hsp90) chaperone
CML66 was previously regarded as a member of the Nuclear distribution gene C (NudC) family because of its conserved domain (Zheng et al, 2011; Riera and Lazo, 2009), further studies are needed to determine whether CML66 plays a role in the regulation of Hsp90 ATPase activity and client protein stability via its p23 domain
Summary
Emerging roles of NudC family: from molecular regulation to clinical implications. Nuclear distribution gene C (NudC) was first found in Aspergillus nidulans as an upstream regulator of NudF, whose mammalian homolog is Lissencephaly 1 (Lis). 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 (Hsp). Our group and the others found that NudC homologs were involved in cell cycle regulation by stabilizing the components of the LIS1/dynein complex. Our data showed that NudCL2 regulates the LIS1/dynein pathway by stabilizing LIS1 with Hsp 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. Nuclear distribution gene C, heat shock protein 90, p23, dynein, Lissencephaly 1, cell cycle, ciliogenesis
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