“…The gene encoding this protein, HnudC, was isolated by homology to the Aspergillus nidulans gene nudC (Miller et al 1999). The nudC gene is one of several in A. nidulans originally identified by complementation of temperature-sensitive nud (nuclear distribution) mutants (Xiang et al 1995a). The nudC gene is one of several in A. nidulans originally identified by complementation of temperature-sensitive nud (nuclear distribution) mutants (Xiang et al 1995a).…”
Section: Introductionmentioning
confidence: 99%
“…At restrictive temperatures for nud mutants, nuclei divide normally but are not transported into growing mycelia. In A. nidulans, the effect of the nudC3 mutation is to inhibit nuclear migration and to reduce colony growth, as do nudA and nudF mutations (Osmani et al 1990;Xiang et al 1995a). NudA encodes a cytoplasmic dynein heavy chain and nudG encodes a dynein light chain (Beckwith and Morris 1995;Xiang et al 1994).…”
Section: Introductionmentioning
confidence: 99%
“…In A. nidulans, five nuclear migration genes have been identified. NudC is thought to act upstream of nudF in A. nidulans, based on genetic and biochemical studies (Chiu and Morris 1995;Morris et al 1998b;Xiang et al 1995a, b) and NUDC has been shown to modulate NUDF protein at a posttranscriptional level (Morris et al 1998b;Xiang et al 1995b). NudF encodes a regulator of an unknown aspect of dynein motor function (Xiang et al 1995b).…”
We recently identified a novel human gene, HnudC, homologous to an Aspergillus nidulans gene coding for a protein crucial to nuclear migration, cell wall morphogenesis, and cell growth. While mRNA for this gene is expressed in most tissues, HNUDC protein expression is highly regulated. To provide insight into the function of this protein, we performed immunohistochemical analysis of the distribution of HNUDC in 19 different human tissues. Intense immunolabeling was observed in proliferating cells, including spermatocytes at all stages, early hematopoietic cells, cortical thymocytes, immunoblasts, and basal colonic and esophageal mucosa. Within a given tissue, cells with different proliferative capacities demonstrated different levels of HNUDC expression. HNUDC was also highly expressed in ciliated epithelia including those found in ependyma, bronchial mucosa, and fallopian tubes. Immunolabeling was moderate in several non-proliferating tissues, but little or no labeling was observed in most other tissues examined. We also demonstrated by western blotting that most cell lines express extremely high levels of HNUDC compared to their normal counterparts. While this supports a role for HnudC in cell proliferation, these data indicate that cell lines are not a reliable measure of HNUDC protein expression in normal tissues. We conclude that HNUDC is highly expressed in cell lines and the proliferating cells of normal tissues, consistent with our hypothesis that HNUDC is conserved throughout evolution for a crucial function in cell division. In addition, the high level in ciliated cells suggests an important role in ciliary motility or assembly, analogous to its role in A. nidulans nuclear movement.
“…The gene encoding this protein, HnudC, was isolated by homology to the Aspergillus nidulans gene nudC (Miller et al 1999). The nudC gene is one of several in A. nidulans originally identified by complementation of temperature-sensitive nud (nuclear distribution) mutants (Xiang et al 1995a). The nudC gene is one of several in A. nidulans originally identified by complementation of temperature-sensitive nud (nuclear distribution) mutants (Xiang et al 1995a).…”
Section: Introductionmentioning
confidence: 99%
“…At restrictive temperatures for nud mutants, nuclei divide normally but are not transported into growing mycelia. In A. nidulans, the effect of the nudC3 mutation is to inhibit nuclear migration and to reduce colony growth, as do nudA and nudF mutations (Osmani et al 1990;Xiang et al 1995a). NudA encodes a cytoplasmic dynein heavy chain and nudG encodes a dynein light chain (Beckwith and Morris 1995;Xiang et al 1994).…”
Section: Introductionmentioning
confidence: 99%
“…In A. nidulans, five nuclear migration genes have been identified. NudC is thought to act upstream of nudF in A. nidulans, based on genetic and biochemical studies (Chiu and Morris 1995;Morris et al 1998b;Xiang et al 1995a, b) and NUDC has been shown to modulate NUDF protein at a posttranscriptional level (Morris et al 1998b;Xiang et al 1995b). NudF encodes a regulator of an unknown aspect of dynein motor function (Xiang et al 1995b).…”
We recently identified a novel human gene, HnudC, homologous to an Aspergillus nidulans gene coding for a protein crucial to nuclear migration, cell wall morphogenesis, and cell growth. While mRNA for this gene is expressed in most tissues, HNUDC protein expression is highly regulated. To provide insight into the function of this protein, we performed immunohistochemical analysis of the distribution of HNUDC in 19 different human tissues. Intense immunolabeling was observed in proliferating cells, including spermatocytes at all stages, early hematopoietic cells, cortical thymocytes, immunoblasts, and basal colonic and esophageal mucosa. Within a given tissue, cells with different proliferative capacities demonstrated different levels of HNUDC expression. HNUDC was also highly expressed in ciliated epithelia including those found in ependyma, bronchial mucosa, and fallopian tubes. Immunolabeling was moderate in several non-proliferating tissues, but little or no labeling was observed in most other tissues examined. We also demonstrated by western blotting that most cell lines express extremely high levels of HNUDC compared to their normal counterparts. While this supports a role for HnudC in cell proliferation, these data indicate that cell lines are not a reliable measure of HNUDC protein expression in normal tissues. We conclude that HNUDC is highly expressed in cell lines and the proliferating cells of normal tissues, consistent with our hypothesis that HNUDC is conserved throughout evolution for a crucial function in cell division. In addition, the high level in ciliated cells suggests an important role in ciliary motility or assembly, analogous to its role in A. nidulans nuclear movement.
“…In filamentous fungal systems the function of dynein is also nonessential. Mutational analyses of dynein components in Aspergillus nidulans (Xiang et al, 1994(Xiang et al, , 1995, as well as Neurospora crassa (Plamann et al, 1994;Bruno et al, 1996), have supported a role for dynein in nuclear migration, but not nuclear divisions. The recent analysis of dynein heavy chain mutations in Nectria haematococca have provided evidence for the action of dynein in microtubule assembly and/or stability at spindle pole bodies and resultant defects in spindle elongation (Inoue et al, 1998).…”
Cytoplasmic dynein is a multisubunit minus-end–directed microtubule motor that serves multiple cellular functions. Genetic studies in Drosophila and mouse have demonstrated that dynein function is essential in metazoan organisms. However, whether the essential function of dynein reflects a mitotic requirement, and what specific mitotic tasks require dynein remains controversial. Drosophila is an excellent genetic system in which to analyze dynein function in mitosis, providing excellent cytology in embryonic and somatic cells. We have used previously characterized recessive lethal mutations in the dynein heavy chain gene, Dhc64C, to reveal the contributions of the dynein motor to mitotic centrosome behavior in the syncytial embryo. Embryos lacking wild-type cytoplasmic dynein heavy chain were analyzed by in vivo analysis of rhodamine-labeled microtubules, as well as by immu-nofluorescence in situ methods. Comparisons between wild-type and Dhc64C mutant embryos reveal that dynein function is required for the attachment and migration of centrosomes along the nuclear envelope during interphase/prophase, and to maintain the attachment of centrosomes to mitotic spindle poles. The disruption of these centrosome attachments in mutant embryos reveals a critical role for dynein function and centrosome positioning in the spatial organization of the syncytial cytoplasm of the developing embryo.
“…The identification of these genes have revealed that they code for light, intermediate and heavy chains of dynein (an actin-associated molecular motor) [1] and ARP1 and p150 components of dynactin complex [2], which regulates dynein (Fig. 1) [3]. Deletions in nudC gene result in a more severe phenotype than other nuclear distribution mutants, profoundly affecting the morphology and composition of the cell wall and resulting in lethality [4].…”
Nuclear distribution gene C homolog (NudC) is a highly conserved gene. It has been identified in different species from fungi to mammals. The high degree of conservation, in special in the nudC domain, suggests that they are genes with essential functions. Most of the identified genes in the family have been implicated in cell division through the regulation of cytoplasmic dynein. As for mammalian genes, human NUDC has been implicated in the migration and proliferation of tumor cells and has therefore been considered a possible therapeutic target. There is evidence suggesting that mammalian NudC is also implicated in the regulation of the inflammatory response and in thrombopoiesis. The presence of these other functions not related to the interaction with molecular motors agrees with that these genes and their products are larger in size than their microbial orthologous, indicating that they have evolved to convey additional features.
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