A new function of Nm23/NDP kinase as a differentiation inhibitory factor, which does not require it's kinase activity

Abstract

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 α and β, recombinant mouse nm23‐M1 and ‐M2, and recombinant human nm23‐H1 and ‐H2 containing a mutant nm23‐H2^His 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.