Disease relevance of NUDC

• In a cDNA phage display screen using Plk1 C-terminal affinity columns, we identified NudC (nuclear distribution gene C) as a Plk1 binding protein [1].
• These results suggest that NudC overexpression led to a block in cell division of prostate cancer cells, and that Ad-NudC may provide a new anticancer drug approach targeting the function of a microtubule motor-associated protein [2].
• Furthermore, HNUDC was significantly enhanced in lysates of bone marrow aspirates from patients with acute myelogenous and acute lymphoblastic leukemia compared to aspirates from normal controls, suggesting that HnudC is involved in malignant hematopoietic cell growth as well [3].
• A significant increase in HNUDC is present in bone marrow aspirates from patients with acute lymphoblastic leukemia (ALL) and acute myelogenous leukemia (AML) compared to the level in normal cellular counterparts, demonstrating dysregulated expression in leukemia [4].

High impact information on NUDC

• A mammalian NudC-like protein essential for dynein stability and cell viability [5].
• Depletion of NudC reduced end-on microtubule attachments at kinetochores and resulted in defects in chromosome congression at the metaphase plate [6].
• NudC is required for Plk1 targeting to the kinetochore and chromosome congression [6].
• Importantly, NudC-deficient cells exhibited mislocalization of Plk1 and the Kinesin-7 motor CENP-E from prometaphase kinetochores [6].
• The interaction of Lis1 with NudC, in conjunction with the MDS and ILS phenotypes, raises the possibility that nuclear movement in the ventricular zone is tied to the specification of neuronal fates and thus to cortical architecture [7].

Biological context of NUDC

• Primers which amplify individual exons of NUDC were developed for mutation analysis [8].
• We have isolated the human NUDC gene and its two processed pseudogenes [8].
• NUDC consists of at least 9 exons ranging from 66 bp to 266 bp in size and 8 introns from 92 bp to 2.0 kb in length, and the total genomic region spans about 8 kb [8].
• These results demonstrate that the LIS-1/NUDC-like proteins of C. elegans represent a link between nuclear positioning, cell division, and neuronal function [9].
• The human NUDC gene is highly conserved and its predicted amino acid sequence shows 94% identity to mouse NudC and 95% identity to rat NudC [8].

Anatomical context of NUDC

• Further, a key mitotic enzyme, polo-like kinase, is mislocalized from the centrosomes and the midbody in NudC altered cells [10].
• In normal human bone marrow, HNUDC protein and mRNA are highly expressed in early myeloid and erythroid precursors and decline as these cells terminally differentiate [3].
• Immunofluorescence staining of human megakaryocyte cells indicated that hNUDC and Mpl colocalized at all stages of megakaryocyte development [11].
• Consistent with its expression in individual neurons, a high level of NudC is detected in regions of the embryonic neocortex undergoing extensive neurogenesis as well as neuronal migration [12].
• We also demonstrated by western blotting that most cell lines express extremely high levels of HNUDC compared to their normal counterparts [13].

Regulatory relationships of NUDC

• These data demonstrate that HNUDC is highly expressed in normal and malignant human hematopoietic precursors and suggest it is of functional importance in the proliferation of these cells [3].

Other interactions of NUDC

• A role for Plk1 phosphorylation of NudC in cytokinesis [1].
• The amino terminus of the larger human protein (HNUDC = 45 kDa) does not overlap with A. nidulans NUDC (22 kDa) [3].

Analytical, diagnostic and therapeutic context of NUDC

• Molecular cloning and characterization of the human NUDC gene [8].
• NUDC was mapped to 1p34-p35 by fluorescence in situ hybridization [8].
• Immunofluorescence microscopy revealed a significant increase in cells with a single enlarged nucleus and cells exhibiting multiple nuclei, along with a concomitant increase in cell size in Ad-NudC-infected cells [2].
• Expression of NudC in DU145 or PC-3 cells inhibited tumor growth in a subcutaneous xenograft model [2].
• In this study, we report the binding of hNUDC to the extracellular domain of the thrombopoietin receptor (Mpl) as detected by the yeast two-hybrid system, GST pull-down, and co-immunoprecipitation [11].

References