Disease relevance of DMTF1

• Further study will be needed to determine whether gene-specific mutations implicate hDMP1 as a tumor suppressor in acute leukemias with deletions of the long arm of chromosome 7 or in other types of human malignancy [1].
• Both Dmp1-null mice and individuals with a newly identified disorder, autosomal recessive hypophosphatemic rickets, manifest rickets and osteomalacia with isolated renal phosphate-wasting associated with elevated fibroblast growth factor 23 (FGF23) levels and normocalciuria [2].
• Loss of DMP1 causes rickets and osteomalacia and identifies a role for osteocytes in mineral metabolism [2].
• DMP1 mutations in autosomal recessive hypophosphatemia implicate a bone matrix protein in the regulation of phosphate homeostasis [3].

High impact information on DMTF1

• Mechanistic studies using Dmp1-null mice demonstrated that absence of DMP1 results in defective osteocyte maturation and increased FGF23 expression, leading to pathological changes in bone mineralization [2].
• Here, we mapped an autosomal recessive form (designated ARHP) to chromosome 4q21 and identified homozygous mutations in DMP1 (dentin matrix protein 1), which encodes a non-collagenous bone matrix protein expressed in osteoblasts and osteocytes [3].
• Dentin matrix protein 1 (encoded by DMP1) is highly expressed in osteocytes and, when deleted in mice, results in a hypomineralized bone phenotype [2].
• DMP1 binds to a single canonical recognition site in the ARF promoter to activate gene expression, and in turn, p19(ARF) synthesis causes p53-dependent cell cycle arrest [4].
• Induction of ARF tumor suppressor gene expression and cell cycle arrest by transcription factor DMP1 [4].

Biological context of DMTF1

• Alternative splicing of the human cyclin D-binding Myb-like protein (hDMP1) yields a truncated protein isoform that alters macrophage differentiation patterns [5].
• The hDMP1 cDNA contains a 2280bp open reading frame that shares a high degree of identity with the mDmp1 coding region [1].
• DMP1 binds to one of the Ets binding sites (designated Ets C) and synergizes with c-Myb in activating CD13/APN expression [6].
• Activation of CD13/APN required both the intact DNA binding and transactivation domains of DMP1 and was inhibited by D-type cyclins, but not by cyclins A, B, C, or H, in a CDK-independent manner [6].
• DMP1 mRNA and protein are ubiquitously expressed throughout the cell cycle in mouse tissues and in representative cell lines [7].

Anatomical context of DMTF1

• The 4.4kb hDMP1 messenger RNA is ubiquitously expressed in normal human tissues, with highest levels in testis and substructures within the brain [1].
• These data indicate that two different Myb family proteins collaborate in regulating APN gene expression and point to a role for DMP1 in normal myeloid cell development [6].
• In this report, we demonstrate that dentin matrix protein 1 (DMP1), which is localized in the nucleus during early differentiation of odontoblasts, is able to bind specifically with the DSPP promoter and activate its transcription [8].
• Real-time PCR analyses of ADM and DMP-1 in a panel of healthy and carious pulpal tissue and also in immune system cells highlighted the heterogeneity of caries and indicated increased expression of ADM in neutrophils activated by bacterial products [9].
• Elevated expression of BSP and OPN, along with a marked decrease of dentin sialoprotein and DMP-1 in RD, suggests a difference in the mechanism of formation of the two forms of dentin [10].

Associations of DMTF1 with chemical compounds

• Both full-length recombinant DMP1 and post-translationally modified native DMP1 were able to nucleate hydroxyapatite (HAP) in the presence of type I collagen [11].
• The group that received two applications of fluoride paste per year had a DMTF increment that was about 24% less than that of the control group; however, the DMFS increment was only 5% less [12].

Other interactions of DMTF1

• We have cloned two novel, alternatively spliced messages of human cyclin D-binding Myb-like protein (hDMP1) [5].

Analytical, diagnostic and therapeutic context of DMTF1

• By use of fluorescence in situ hybridization with a human genomic P1 probe, we assigned hDMP1 to chromosome 7, band q21 [1].
• A chromatin immunoprecipitation assay confirmed the in vivo association of DMP1 with the DSPP promoter [8].
• ELISA results revealed a significant difference in the concentrations of DMP1, PP and DSP between control and root resorption groups [13].
• According to a sample size calculation a sample size of 200 GPs (each GP including 20 patients) will be required for the comparison of DMP 1 and DMP 2 considering possible drop-outs [14].

References