Role for NudC, a dynein-associated nuclear movement protein, in mitosis and cytokinesis

Abstract

NudC, a nuclear movement protein that associates with dynein, was originally cloned as a mitogen-inducible early growth response gene. NudC forms a biochemical complex with components of the dynein/dynactin complex and is suggested to play a role in translocation of nuclei in proliferating neuronal progenitors as well as in migrating neurons in culture. Here, we show that NudC plays multiple roles in mitosis and cytokinesis in cultured mammalian cells. Altering NudC levels by either small interfering RNA-mediated gene silencing or adenovirus-mediated overexpression resulted in multinucleated cells and cells with persistent intercellular connections and disorganized midzone and midbody matrix. These phenotypes suggest a failure in cytokinesis in NudC altered cells. Further, a key mitotic enzyme, polo-like kinase, is mislocalized from the centrosomes and the midbody in NudC altered cells. Gene silencing of nud-1, the Caenorhabditis elegansortholog of NudC, led to a loss of midzone microtubules and the rapid regression of the cleavage furrow, which resulted in one-celled embryos containing two nuclei. The loss of midzone microtubule organization owing to silencing of the NudC/nud-1 gene in two systems, coupled with the loss of Plk1 from mitotic structures in mammalian cells, provide clues to the cytokinesis defect and the multinucleation phenotype. Our findings suggest that NudC functions in mitosis and cytokinesis, in part by regulating microtubule organization at the midzone and midbody.

NudC-like protein 2 regulates the LIS1/dynein pathway by stabilizing LIS1 with Hsp90

“…These data indicate that nudC may be upstream of nudF in A. nidulans. In mammals, we and other groups have found that NudC associates with LIS1 and the cytoplasmic dynein complex and influences the dynein's function (16,17); however, there is no report supporting a direct role of NudC in the regulation of LIS1. Recently, we showed that a mammalian NudC-like protein, NudCL, is required specifically for the stabilization of dynein intermediate chain, but not LIS1 (18).…”

“…In mammals, there are at least three homologs to Aspergillus NudC: NudC, NudCL, and NudCL2. We and other groups have found that NudC is involved in cell cycle progression via phosphorylation by Polo-like kinase 1, a key mitotic kinase (16,17,35). NudC is shown to associate with the LIS1/dynein complex (36); however, the function of this interaction was still uncharacterized.…”

NudC regulates actin dynamics and ciliogenesis by stabilizing cofilin 1

“…We and other groups have found that NudC plays crucial roles in diverse cellular processes, including cell division and neuronal migration, partially by modulating the dynein complex [13][14][15]. A growing body of evidence implies that NudC functions as a co-chaperone of Hsp90 to stabilize client proteins [16][17][18].…”

Polyploidization and Cancer

“…231 A recent proteomic screen identified a large number of proteins that bind to the Polo-box domain of Plk1, including the Rho kinase ROCK2, 253 where Plk1 and RhoA may function together to enhance ROCK2 activity. Another substrate of Plk1 that may be involved in regulation of mitosis and cytokinesis is NudC, 254,255 a dynein/dynactin associated protein that is essential for midzone formation and cytokinesis completion in C. elegans and mammalian cells. 257 as well as centrosome amplification, 258 suggesting that increased expression of Plk1 observed in some tumors may have an effect on cytokinesis completion as well as chromosome segregation.…”