A homolog of the fungal nuclear migration gene nudC is involved in normal and malignant human hematopoiesis.
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.
Miller
B A
BA
Department of Pediatrics, The Pennsylvania State University College of Medicine, The Milton S. Hershey Medical Center, Hershey 17033-0850, USA. bam11@psu.edu
Zhang
M Y
MY
Gocke
C D
CD
De Souza
C
C
Osmani
A H
AH
Lynch
C
C
Davies
J
J
Bell
L
L
Osmani
S A
SA
D000918:Antibody Specificity; D001233:Aspergillus nidulans / Q000235:genetics; D001854:Bone Marrow Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D018797:Cell Cycle Proteins; D002454:Cell Differentiation / Q000235:genetics; D002455:Cell Division / Q000235:genetics; D003001:Cloning, Molecular; D005656:Fungal Proteins / Q000235:genetics* / Q000276:immunology; D015870:Gene Expression; D005800:Genes, Fungal / Q000235:genetics*; D005816:Genetic Complementation Test; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000494:pharmacology; D006410:Hematopoiesis / Q000235:genetics*; D006801:Humans; D007231:Infant, Newborn; D015470:Leukemia, Myeloid, Acute / Q000378:metabolism; D008969:Molecular Sequence Data; D009687:Nuclear Proteins; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000378:metabolism; D011506:Proteins / Q000235:genetics* / Q000502:physiology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017386:Sequence Homology, Amino Acid; D014407:Tumor Cells, Cultured
D018797:Cell Cycle Proteins; D005656:Fungal Proteins; C094005:NUDC protein, Emericella nidulans; C512648:NUDC protein, human; D009687:Nuclear Proteins; D011506:Proteins; D016178:Granulocyte-Macrophage Colony-Stimulating Factor