Disease relevance of Cart1

• Prenatal folic acid treatment suppresses acrania and meroanencephaly in mice mutant for the Cart1 homeobox gene [1].
• Cart-1 cDNA was recently cloned from a rat chondrosarcoma tumor and it encodes a protein containing a paired-like homeodomain that is selectively expressed in cartilage during early chondrocyte differentiation [2].

High impact information on Cart1

• Prenatal treatment of Cart1 homozygous mutants with folic acid suppresses the development of the acrania/meroanencephaly phenotype [1].
• Developmental studies suggest that Cart1 is required for forebrain mesenchyme survival and that its absence disrupts cranial neural tube morphogenesis by blocking the initiation of closure in the midbrain region that ultimately leads to the generation of lethal craniofacial defects [1].
• NTD risk is reduced in various models by different maternal nutrient supplements, including folic acid ( Pax3, Cart1, Cd mutants), inositol ( ct ) and methionine ( Axd ) [3].
• Alx4 and Cart1 are co-expressed at several sites during development, including the craniofacial mesenchyme, the mesenchymal derivatives of neural crest cells in the first branchial arch and the limb bud mesenchyme [4].
• First, mutation of Cart1 exacerbates Alx4-dependent polydactyly in a manner that is dependent on gene dosage [4].

Biological context of Cart1

• In vitro acetylation assay was performed with the recombinant p300-HAT domain and Cart1 in the presence of acetyl-CoA [5].
• INTRODUCTION: Cart1 encodes a paired-like homeoprotein expressed selectively in chondrocyte lineage during embryonic development [5].
• METHODS: To study the transcription activity of Cart1, a reporter construct containing a putative Cart1 binding site was transiently transfected with the expression vectors of each protein [5].
• Although its target gene remains unknown, gene disruption studies have revealed that Cart1 plays an important role for craniofacial bone formation as well as limb development by cooperating with another homeoprotein, Alx4 [5].
• Acetylation of this residue increases the interaction between p300/CBP and Cart1 and enhances its transcriptional activation [5].

Anatomical context of Cart1

• In early embryos, Cart-1 RNA was detected at high levels in head mesenchyme, lateral mesoderm, sclerotomes and limb bud mesenchyme [6].
• In addition, Cart-1 RNA was also found in lung buds, tendons and mesonephros [6].
• The Cart-1 gene was localized to human chromosome 12 and regionally mapped to the 12q21.3-q22 by PCR analysis of rodent-X-human somatic cell hybrid DNA and the CEPH megabase-insert YAC DNA pools, respectively [2].
• Taken together, these data indicate that Cart-1 may also influence cervix development, identify a putative DNA binding site for Cart-1, and, begin to define its functional role as modulator of gene expression [2].
• Northern and reverse transcriptase polymerase chain reaction (RT-PCR) analysis revealed Cart-1 mRNA expression in HeLa cervical carcinoma cells and human cervical tissue, but Cart-1 mRNA was not detected in GH3 rat pituitary cells and murine 10T1/2 one-half fibroblast cells [2].

Associations of Cart1 with chemical compounds

• We describe here that the general coactivator p300/CBP controls the transcription activity of Cart1 through acetylation of a lysine residue that is highly conserved in other homeoproteins [5].
• In genetic NTD models such as Cart1, splotch, Cited2, and crooked tail, and NTD induced by teratogens including valproic acid and fumonisins, the incidence of defects is reduced by maternal folic acid supplementation [7].
• Considering that oxidative stress and inflammation may persist for a prolonged period after stent placement, treatment with AGI-1067 for the entire period of risk after percutaneous coronary intervention (PCI) [instead of only 4 weeks in CART-1] may result in enhanced protection against luminal renarrowing [8].

Other interactions of Cart1

• Linking the Cart1 aristaless domain to Alx3 extinguishes teratogenicity [9].
• The transcription factors Sox9, Og12, and Cart-1 did not affect the promoter activity [10].
• The gene for Cart-1 was mapped to a segment of mouse chromosome 10 between the genes for phenylalanine hydroxylase and interferon gamma [6].

Analytical, diagnostic and therapeutic context of Cart1

• Confocal microscopy analysis shows that Cart1 recruits overexpressed and endogenous p300 to a Cart1-specific subnuclear compartment [5].
• Northern blot analysis of the transcription factors Cart-1 and Sox-9 indicated maximum mRNA levels at E12.5 then a decreased expression during the following days of gestation [11].
• Here we report the molecular cloning of the human Cart-1 cDNA from a HeLa cervical carcinoma cDNA library [2].

References