Disease relevance of NME3

• These results are consistent with a role for DR-nm23 in normal hematopoiesis and raise the possibility that its overexpression contributes to differentiation arrest, a feature of blastic transformation in chronic myelogenous leukemia [1].
• We have identified a cDNA clone, DR-nm23, differentially expressed in a blast-crisis cDNA library, which has approximately 70% sequence similarity to the putative metastatic suppressor genes, nm23-H1 and nm23-H2 [1].
• We have now found that the expression of DR-nm23 is not restricted to hematopoietic cells but is also detected in an array of solid tumor cell lines, including carcinoma of the breast, colon, and prostate, as well as the glioblastoma cell line T98G [2].

High impact information on NME3

• RESULTS: DR-nm23 messenger RNA levels in nontransfected LAN-5 and SK-N-SH cells generally increased with time after exposure to differentiation-inducing conditions; levels of the other two human nm23 messenger RNAs (nm23-H1 and nm23-H2) remained essentially constant [3].
• Transfected SK-N-SH cells overexpressing DR-nm23 exhibited some characteristics of differentiated cells (increased vimentin and collagen type IV expression) even in the absence of differentiation-inducing conditions [3].
• CONCLUSIONS: DR-nm23 gene expression appears to be associated with differentiation in neuroblastoma cells and may affect cellular adhesion through regulation of integrin protein expression [3].
• Overexpression of DR-nm23, a protein encoded by a member of the nm23 gene family, inhibits granulocyte differentiation and induces apoptosis in 32Dc13 myeloid cells [1].
• In this study, we show that mutations in the catalytic domain and in the serine 61 phosphorylation site, possibly required for protein-protein interactions, impair the ability of DR-nm23 to induce neural differentiation [4].

Biological context of NME3

• We have also isolated both the gene and its 5'-flanking region and found that DR-nm23 localizes on chromosome 16q13 [2].
• The 5'-flanking region of DR-nm23 does not contain a canonical TATA box or a CAAT box, but it is G+C rich and contains two binding sites for the developmentally regulated transcription factor activator protein 2 (AP-2) [2].
• Moreover, AP-2 induced a 3-fold transactivation of the DR-nm23 5'-flanking segment from nucleotides -1676 to +123 and interacted specifically with oligomers containing putative AP-2 binding sites (-936 to -909, and -548 to -519) as indicated by electrophoretic mobility shift assay [2].
• RESULTS: In several cell lines, overexpression of DR-nm23 was associated with more differentiated phenotypes [5].
• DR-nm23 expression affects neuroblastoma cell differentiation, integrin expression, and adhesion characteristics [5].

Anatomical context of NME3

• Transient expression assays of DR-nm23 promoter-chloramphenicol acetyltransferase constructs demonstrated that the segment from nucleotides -1028 to +123 has the highest activity in hematopoietic K562 cells and in TK-ts13 hamster fibroblasts [2].

Associations of NME3 with chemical compounds

• DR-nm23 gene expression in neuroblastoma cells: relationship to integrin expression, adhesion characteristics, and differentiation [3].
• In co-immunoprecipitation experiments, wild-type DR-nm23 binds other members of nm23 family, but mutations in the catalytic and in the RGD domains and in serine 61 inhibit the formation of hetero-multimers [4].
• DR-nm23 expression increased after retinoic acid induction of differentiation in human cell lines SK-N-SH and LAN-5 [5].

References