TY - JOUR
T1 - A homolog of the fungal nuclear migration gene nudC is involved in normal and malignant human hematopoiesis
AU - Miller, Barbara A.
AU - Zhang, Min Ying
AU - Gocke, Christopher D.
AU - De Souza, Colin
AU - Osmani, Aysha H.
AU - Lynch, Christopher
AU - Davies, Jonathan
AU - Bell, Laurie
AU - Osmani, Stephen A.
N1 - Funding Information:
The authors would like to thank Dr. Li-Yuan Yu-Lee for helpful discussions about rat nudC. They are grateful to Dr. Toshio Kitamura for providing TF-1 cells, Dr. Ross Hannan for help with Northern blotting, Dr. Shao-Cong Sun for providing the IκBα antibody, Jan Rambler and Xiao-Hong Wang for performing immunohistochemistry, and Carol Stine for culture of cell lines. The authors would like to thank Tina Eberly and Maxine Gerberich for careful preparation of the manuscript. This work was supported by National Institutes of Health Grants R01 DK 46778 (B.A.M.), M01 RR10732 (GCRC grant), and R01 GM 42564 (S.A.O.). This work also was supported by the Penn State Cancer Center Research Grant Program and by the Four Diamonds Fund. B.A.M. is the recipient of an American Cancer Society Faculty Research Award.
PY - 1999/4
Y1 - 1999/4
N2 - The filamentous fungus Aspergillus nidulans nudC gene has an essential function in movement of nuclei following mitosis and is required for normal colony growth. Here, the molecular cloning and role in hematopoiesis of a human gene (designated HnudC) homologous to A. nidulans nudC is reported. The amino terminus of the larger human protein (HNUDC = 45 kDa) does not overlap with A. nidulans NUDC (22 kDa). However, NUDC and the C-terminal 94 amino acids of HNUDC are 67% identical. The C-terminal region of the HnudC gene fully complements the A. nidulans temperature-sensitive nudC3 mutation, suggesting that nudC has an essential function in cell growth that is conserved from filamentous fungi to humans. In initial studies, HNUDC levels were much higher in erythroid precursors compared to most other human tissues. Therefore, the potential role of HnudC in hematopoiesis was explored. 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. To determine whether hematopoietic growth factors induce HnudC expression, TF-1 cells were stimulated by granulocyte- macrophage colony-stimulating factor. This induced a significant increase in HNUDC protein and HnudC mRNA, suggesting that enhancement of HnudC expression in response to growth factor stimulation may be mediated at the transcription level. 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. 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.
AB - The filamentous fungus Aspergillus nidulans nudC gene has an essential function in movement of nuclei following mitosis and is required for normal colony growth. Here, the molecular cloning and role in hematopoiesis of a human gene (designated HnudC) homologous to A. nidulans nudC is reported. The amino terminus of the larger human protein (HNUDC = 45 kDa) does not overlap with A. nidulans NUDC (22 kDa). However, NUDC and the C-terminal 94 amino acids of HNUDC are 67% identical. The C-terminal region of the HnudC gene fully complements the A. nidulans temperature-sensitive nudC3 mutation, suggesting that nudC has an essential function in cell growth that is conserved from filamentous fungi to humans. In initial studies, HNUDC levels were much higher in erythroid precursors compared to most other human tissues. Therefore, the potential role of HnudC in hematopoiesis was explored. 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. To determine whether hematopoietic growth factors induce HnudC expression, TF-1 cells were stimulated by granulocyte- macrophage colony-stimulating factor. This induced a significant increase in HNUDC protein and HnudC mRNA, suggesting that enhancement of HnudC expression in response to growth factor stimulation may be mediated at the transcription level. 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. 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.
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U2 - 10.1016/S0301-472X(98)00074-5
DO - 10.1016/S0301-472X(98)00074-5
M3 - Article
C2 - 10210332
AN - SCOPUS:0032957638
SN - 0301-472X
VL - 27
SP - 742
EP - 750
JO - Experimental Hematology
JF - Experimental Hematology
IS - 4
ER -