A new function of Nm23/NDP kinase as a differentiation inhibitory factor, which does not require it's kinase activity.
We recently identified a differentiation inhibiting factor (I-factor) in mouse myeloid leukemia M1 cells as a murine homolog of nm23-H2/nucleoside diphosphate kinase (NDPK)-B gene product. We examined the I-factor activities of several authentic nm23/NDPK proteins, i.e. recombinant rat NDPK alpha and beta, recombinant mouse nm23-M1 and -M2, and recombinant human nm23-H1 and -H2 containing a mutant nm23-H2His protein lacing NDPK activity. Almost all these nm23/NDPK proteins showed I-factor activity. Moreover, to understand the active domain exhibiting I-factor activity of nm23-H2 protein lacking NDPK activity, we have investigated the I-factor activities of some truncated nm23-H2 proteins. The truncated nm23-H2 protein containing N-terminal peptide 1-60 retained the I-factor activity. These results provide the first evidence for a function of nm23/NDPK as a differentiation inhibiting factor in leukemic cells, that is independent of its NDPK activity and dependent on the presence of N-terminal peptide.
Okabe-Kado
J
J
Department of Chemotherapy, Saitama Cancer Center Research Institute, Japan.
Kasukabe
T
T
Hozumi
M
M
Honma
Y
Y
Kimura
N
N
Baba
H
H
Urano
T
T
Shiku
H
H
D000818:Animals; D001483:Base Sequence; D015415:Biomarkers; D002454:Cell Differentiation / Q000187:drug effects*; D017931:DNA Primers / Q000737:chemistry; D006801:Humans; D007951:Leukemia, Myeloid; D051379:Mice; D008969:Molecular Sequence Data; D020559:Monomeric GTP-Binding Proteins; D054778:NM23 Nucleoside Diphosphate Kinases; D009701:Nucleoside-Diphosphate Kinase; D051381:Rats; D011994:Recombinant Proteins; D017384:Sequence Deletion; D013329:Structure-Activity Relationship; D014157:Transcription Factors / Q000494:pharmacology*; D014407:Tumor Cells, Cultured / Q000166:cytology
D015415:Biomarkers; D017931:DNA Primers; D054778:NM23 Nucleoside Diphosphate Kinases; D011994:Recombinant Proteins; D014157:Transcription Factors; C517938:NME1 protein, human; C517939:Nme1 protein, mouse; D009701:Nucleoside-Diphosphate Kinase; D020559:Monomeric GTP-Binding Proteins