A NEW FUNCTION OF NM23 NDP KINASE AS A DIFFERENTIATION INHIBITORY FACTOR, WHICH DOES NOT REQUIRE ITS KINASE-ACTIVITY/

We recently identified a differentiation inhibiting factor (I-factor) in mouse myeloid leukemia M1 cells as a murine homolog of nm23-H2/nucl eoside diphosphate kinase (NDPK)-B gene product, We examined the I-fac tor activities of several authentic nm23/NDPK proteins, i,e recombinan t rat NDPK alpha and beta, recombinant mouse nm23-M1 and -M2, and reco mbinant human nm23-H1 and -H2 containing a mutant nm23-H2(His) protein lacing NDPK activity, Almost all these nm23/NDPK proteins showed I-fa ctor activity. Moreover, to understand the active domain exhibiting I- factor activity of nm23-H2 protein lacking NDPK activity, we have inve stigated the I-factor activities of some truncated nm23-H2 proteins, T he truncated nm23-H2 protein containing N-terminal peptide 1-60 retain ed the I-factor activity, These results provide the first evidence for a function of nm23/NDPK as a differentiation inhibiting factor in leu kemic cells, that is independent of its NDPK activity and dependent on the presence of N-terminal peptide.