A homolog of the fungal nuclear migration gene nudC is involved in normal and malignant human hematopoiesis

The filamentous fungus Alspergillus nidulans nudC gene has an essential fun ction in movement of nuclei following mitosis and is required for normal co lony growth. Here, the molecular cloning and role in hematopoiesis of a hum an gene (designated HnudC) homologous to,A nidulans nudC is reported. The a mino 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 f ully complements the A. nidulans temperature-sensitive nudC3 mutation, sugg esting that nudC has an essential function in cell growth that is conserved from filamentous fungi to humans, In initial studies, HNUDC levels were mu ch higher in erythroid precursors compared to most other human tissues. The refore, the potential role of HnudC in hematopoiesis was explored, In norma l human bone marrow, HNUDC protein and mRNA are highly expressed in early m yeloid and erythroid precursors and decline as these cells terminally diffe rentiate. To determine whether hematopoietic growth factors induce HnudC ex pression, TF-I cells were stimulated by granulocyte-macrophage colony-stimu lating factor. This induced a significant increase in HNUDC protein and Hnu dC mRNA, suggesting that enhancement of HnudC expression in response to gro wth factor stimulation may be mediated at the transcription level. Furtherm ore, HNUDC was significantly enhanced in lysates of bone marrow aspirates f rom patients with acute myelogenous and acute lymphoblastic leukemia compar ed to aspirates from normal controls, suggesting that HnudC is involved in malignant hematopoietic cell growth as well. These data demonstrate that HN UDC is highly expressed in normal and malignant human hematopoietic precurs ors and suggest it is of functional importance in the proliferation of thes e cells. (C) 1999 International Society for Experimenal Hematology. Publish ed by Elsevier Science Inc.