PMID- 10837140 OWN - NLM STAT- MEDLINE DCOM- 20000816 LR - 20031114 IS - 0014-4827 (Print) IS - 0014-4827 (Linking) VI - 257 IP - 2 DP - 2000 Jun 15 TI - The nucleoside diphosphate kinase activity of DRnm23 is not required for inhibition of differentiation and induction of apoptosis in 32Dcl3 myeloid precursor cells. PG - 265-71 AB - DRnm23 belongs to a multigene family which includes nm23-H1, the first bona fide metastasis suppressor gene, nm23-H2, nm23-H4, and nm23-H5. Like nm23-H1, nm23-H2, and nm23-H4, DRnm23 possesses nucleoside diphosphate kinase (NDPK) activity. Upon overexpression in myeloid precursor 32Dcl3 cells, DRnm23 inhibits granulocytic differentiation and promotes apoptosis. Two specific mutants of DRnm23 (H134Q and S136P), at residues required for the NDPK activity, inhibit differentiation and promote apoptosis of 32Dcl3 cells. By contrast, substitution of serine 61 with proline (S61P) or deletion of the RGD domain (DeltaRGD) abrogates the effects of wild-type DRnm23. Like wild-type DRnm23, all four mutants show a predominantly mitochondrial subcellular localization. These studies indicate that the enzymatic activity of DRnm23 is not required for the effects observed in 32Dcl3 cells. Moreover, the inability of the S61P and DeltaRGD DRnm23 mutants to inhibit differentiation and promote apoptosis may be due to defective protein-protein interactions at the mitochondria, the predominant site of DRnm23 subcellular localization. CI - Copyright 2000 Academic Press. FAU - Venturelli, D AU - Venturelli D AD - Department of Microbiology and Immunology, Thomas Jefferson University, Philadelphia, Pennsylvania, 19107, USA. FAU - Cesi, V AU - Cesi V FAU - Ransac, S AU - Ransac S FAU - Engelhard, A AU - Engelhard A FAU - Perrotti, D AU - Perrotti D FAU - Calabretta, B AU - Calabretta B LA - eng PT - Journal Article PL - United States TA - Exp Cell Res JT - Experimental cell research JID - 0373226 RN - EC 2.7.4.6 (Nucleoside-Diphosphate Kinase) SB - IM MH - Animals MH - *Apoptosis MH - Cell Differentiation MH - Cell Line MH - Cell Survival MH - Gene Expression MH - Granulocytes/*cytology MH - Hematopoietic Stem Cells/*cytology/enzymology MH - Mice MH - Mutagenesis MH - Nucleoside-Diphosphate Kinase/genetics/*metabolism MH - Subcellular Fractions MH - Transfection EDAT- 2000/06/06 09:00 MHDA- 2000/08/19 11:00 CRDT- 2000/06/06 09:00 PHST- 2000/06/06 09:00 [pubmed] PHST- 2000/08/19 11:00 [medline] PHST- 2000/06/06 09:00 [entrez] AID - S0014-4827(00)94899-7 [pii] AID - 10.1006/excr.2000.4899 [doi] PST - ppublish SO - Exp Cell Res. 2000 Jun 15;257(2):265-71. doi: 10.1006/excr.2000.4899.