Chromosomal localization and nucleoside diphosphate kinase activity of human metastasis-suppressor genes NM23-1 and NM23-2.
Human metastasis-suppressor genes nm23-1 (NME1) and nm23-2 (NME2) are implicated in control of the metastatic potential of malignant cells. Using somatic cell hybrid analysis and fluorescence in situ hybridization we co-localized both genes to 17q21.3. The 17q21 region carries the locus responsible for early-onset familial breast-ovarian cancer and several other genes that are involved in tumorigenesis and differentiation and undergo frequent rearrangements during neoplastic development. Thus, our mapping places the NME genes in a region that may be subjected to multiple selection pressures. NME1 and NME2 genes were expressed as soluble proteins in a T7 bacterial expression system. Both proteins are independently active nucleotide diphosphate kinases and readily form intra- and intermolecular disulfide bonds. The biochemical properties of these proteins may explain the diversity of mature eucaryotic nucleoside diphosphate kinases.
Molecular Biology Research Section, Lederle Laboratories, American Cyanamid Company, Pearl River, New York 10965.
J M
JM
Backer
C E
CE
Mendola
I
I
Kovesdi
J L
JL
Fairhurst
B
B
O'Hara
R L
RL
Eddy
T B
TB
Shows
S
S
Mathew
V V
VV
Murty
R S
RS
Chaganti
D000818:Animals; D001483:Base Sequence; D002874:Chromosome Mapping; D016147:Genes, Tumor Suppressor; D006801:Humans; D051379:Mice; D008969:Molecular Sequence Data; D009362:Neoplasm Metastasis; D009701:Nucleoside-Diphosphate Kinase / Q000032:analysis*; D011994:Recombinant Proteins / Q000032:analysis
D011994:Recombinant Proteins; D009701:Nucleoside-Diphosphate Kinase