Transcriptional activator that acts at a palindromic recognition sequence to enhance the activity of the SV40 and TK promoters. Functions as a repressor with the prolactin promoter in vivo. May play a role in chondrocyte differentiation and may also influence cervix development.
Homeodomain proteins play important roles in animal development by controlling the expression of genes involved in determining cell fates. The recently cloned human Cart1 gene encodes a paired-class homeodomain (hCART1), whose rodent homolog is mainly expressed in early chondrocytes and in prechondrocytic mesenchymal cells. To better understand its role as a transcription factor, the author has selected specific hCART1 binding sites from a random pool of oligonucleotides. It is reported here that all sites obtained contain a palindrome consisting of two TAAT sequences separated by three or four base pairs. In electromobility shift assays, recombinant hCART1 proteins bind to a palindromic probe as a multimer, possibly a homodimer. In transient transfection assays, hCART1 activates transcription from reporter plasmids containing hCART1 binding sites in HeLa cells, demonstrating both site-dependence and dosage-dependence. It is also shown here that hCART1 localizes to nucleus. These data indicate that hCART1 is a sequence-specific transcription activator in HeLa cells. In combination with data from previous studies in which hCART1 represses transcription in different cell types and promoters, they suggest that hCART1 may be a transcription modulator with both repression and activation activities.
Interacting selectively and non-covalently with any protein or protein complex (a complex of two or more proteins that may include other nonprotein molecules).
Evidence
1:
Inferred from Physical InteractionIntAct
Systematic mapping of protein-protein interactions, or 'interactome' mapping, was initiated in model organisms, starting with defined biological processes and then expanding to the scale of the proteome. Although far from complete, such maps have revealed global topological and dynamic features of interactome networks that relate to known biological properties, suggesting that a human interactome map will provide insight into development and disease mechanisms at a systems level. Here we describe an initial version of a proteome-scale map of human binary protein-protein interactions. Using a stringent, high-throughput yeast two-hybrid system, we tested pairwise interactions among the products of approximately 8,100 currently available Gateway-cloned open reading frames and detected approximately 2,800 interactions. This data set, called CCSB-HI1, has a verification rate of approximately 78% as revealed by an independent co-affinity purification assay, and correlates significantly with other biological attributes. The CCSB-HI1 data set increases by approximately 70% the set of available binary interactions within the tested space and reveals more than 300 new connections to over 100 disease-associated proteins. This work represents an important step towards a systematic and comprehensive human interactome project.
Interacting selectively and non-covalently with DNA of a specific nucleotide composition, e.g. GC-rich DNA binding, or with a specific sequence motif or type of DNA e.g. promotor binding or rDNA binding.
IEAOrtholog Compara
Sequence-specific DNA binding transcription factor activitydefinition[GO:0003700]‹silver
Interacting selectively and non-covalently with a specific DNA sequence in order to modulate transcription. The transcription factor may or may not also interact selectively with a protein or macromolecular complex.
Interacting selectively and non-covalently with a repressing transcription factor and also with the basal transcription machinery in order to stop, prevent, or reduce the frequency, rate or extent of transcription. Cofactors generally do not bind DNA, but rather mediate protein-protein interactions between repressive transcription factors and the basal transcription machinery.
Homeoproteins control cell fates during development, specifying pattern formation and the ontogeny of specific tissues and organs in embryogenesis. 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. Here we report the molecular cloning of the human Cart-1 cDNA from a HeLa cervical carcinoma cDNA library. The human Cart-1 cDNA sequence is 88% identical and the deduced amino acid sequence is 95% identical to the rat sequence, indicating that Cart-1 structure is highly conserved. 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. 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. The Holt-Oram syndrome, characterized by upper limb and atrial septal dysplasias, also maps to the 12q21.3-q22 region. Cotransfection studies show that Cart-1 inhibits the rat prolactin promoter and that this repression is mediated by footprint II, an AT-rich element that functions as an inhibitory site of prolactin gene expression in nonpituitary cells and which was used to clone Cart-1. 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.
The regionalization process in which specific areas of cell differentiation are determined along the anterior-posterior axis. The anterior-posterior axis is defined by a line that runs from the head or mouth of an organism to the tail or opposite end of the organism.
The process whose specific outcome is the progression of the brain over time, from its formation to the mature structure. Brain development begins with patterning events in the neural tube and ends with the mature structure that is the center of thought and emotion. The brain is responsible for the coordination and control of bodily activities and the interpretation of information from the senses (sight, hearing, smell, etc.).
The paired-class homeobox-containing gene, Cart1, is expressed in forebrain mesenchyme, branchial arches, limb buds and cartilages during embryogenesis. Here, we show that Cart1-homozygous mutant mice are born alive with acrania and meroanencephaly but die soon after birth-a phenotype that strikingly resembles a corresponding human syndrome caused by a neural tube closure defect. 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. Prenatal treatment of Cart1 homozygous mutants with folic acid suppresses the development of the acrania/meroanencephaly phenotype.
Homeoproteins control cell fates during development, specifying pattern formation and the ontogeny of specific tissues and organs in embryogenesis. 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. Here we report the molecular cloning of the human Cart-1 cDNA from a HeLa cervical carcinoma cDNA library. The human Cart-1 cDNA sequence is 88% identical and the deduced amino acid sequence is 95% identical to the rat sequence, indicating that Cart-1 structure is highly conserved. 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. 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. The Holt-Oram syndrome, characterized by upper limb and atrial septal dysplasias, also maps to the 12q21.3-q22 region. Cotransfection studies show that Cart-1 inhibits the rat prolactin promoter and that this repression is mediated by footprint II, an AT-rich element that functions as an inhibitory site of prolactin gene expression in nonpituitary cells and which was used to clone Cart-1. 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.
The process, occurring in the embryo, by which the anatomical structures of the limb are generated and organized. A limb is an appendage of an animal used for locomotion or grasping.
The process aimed at the progression of a mesenchymal cell over time, from initial commitment of the cell to its specific fate, to the fully functional differentiated cell.
The biological process whose specific outcome is the progression of a multicellular organism over time from an initial condition (e.g. a zygote or a young adult) to a later condition (e.g. a multicellular animal or an aged adult).
Homeoproteins control cell fates during development, specifying pattern formation and the ontogeny of specific tissues and organs in embryogenesis. 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. Here we report the molecular cloning of the human Cart-1 cDNA from a HeLa cervical carcinoma cDNA library. The human Cart-1 cDNA sequence is 88% identical and the deduced amino acid sequence is 95% identical to the rat sequence, indicating that Cart-1 structure is highly conserved. 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. 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. The Holt-Oram syndrome, characterized by upper limb and atrial septal dysplasias, also maps to the 12q21.3-q22 region. Cotransfection studies show that Cart-1 inhibits the rat prolactin promoter and that this repression is mediated by footprint II, an AT-rich element that functions as an inhibitory site of prolactin gene expression in nonpituitary cells and which was used to clone Cart-1. 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.
Homeoproteins control cell fates during development, specifying pattern formation and the ontogeny of specific tissues and organs in embryogenesis. 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. Here we report the molecular cloning of the human Cart-1 cDNA from a HeLa cervical carcinoma cDNA library. The human Cart-1 cDNA sequence is 88% identical and the deduced amino acid sequence is 95% identical to the rat sequence, indicating that Cart-1 structure is highly conserved. 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. 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. The Holt-Oram syndrome, characterized by upper limb and atrial septal dysplasias, also maps to the 12q21.3-q22 region. Cotransfection studies show that Cart-1 inhibits the rat prolactin promoter and that this repression is mediated by footprint II, an AT-rich element that functions as an inhibitory site of prolactin gene expression in nonpituitary cells and which was used to clone Cart-1. 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.
The biological process whose specific outcome is the progression of the palate from an initial condition to its mature state. This process begins with the formation of the structure and ends with the mature structure. The palate is the partition that separates the nasal and oral cavities.
IEAOrtholog Compara
Positive regulation of transcription from RNA polymerase II promoterdefinition[GO:0045944]‹silver
Any process that activates or increases the frequency, rate or extent of transcription from an RNA polymerase II promoter.
Homeodomain proteins play important roles in animal development by controlling the expression of genes involved in determining cell fates. The recently cloned human Cart1 gene encodes a paired-class homeodomain (hCART1), whose rodent homolog is mainly expressed in early chondrocytes and in prechondrocytic mesenchymal cells. To better understand its role as a transcription factor, the author has selected specific hCART1 binding sites from a random pool of oligonucleotides. It is reported here that all sites obtained contain a palindrome consisting of two TAAT sequences separated by three or four base pairs. In electromobility shift assays, recombinant hCART1 proteins bind to a palindromic probe as a multimer, possibly a homodimer. In transient transfection assays, hCART1 activates transcription from reporter plasmids containing hCART1 binding sites in HeLa cells, demonstrating both site-dependence and dosage-dependence. It is also shown here that hCART1 localizes to nucleus. These data indicate that hCART1 is a sequence-specific transcription activator in HeLa cells. In combination with data from previous studies in which hCART1 represses transcription in different cell types and promoters, they suggest that hCART1 may be a transcription modulator with both repression and activation activities.
The synthesis of RNA from a DNA template by RNA polymerase II, originating at an RNA polymerase II promoter. Includes transcription of messenger RNA (mRNA) and certain small nuclear RNAs (snRNAs).
Homeoproteins control cell fates during development, specifying pattern formation and the ontogeny of specific tissues and organs in embryogenesis. 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. Here we report the molecular cloning of the human Cart-1 cDNA from a HeLa cervical carcinoma cDNA library. The human Cart-1 cDNA sequence is 88% identical and the deduced amino acid sequence is 95% identical to the rat sequence, indicating that Cart-1 structure is highly conserved. 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. 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. The Holt-Oram syndrome, characterized by upper limb and atrial septal dysplasias, also maps to the 12q21.3-q22 region. Cotransfection studies show that Cart-1 inhibits the rat prolactin promoter and that this repression is mediated by footprint II, an AT-rich element that functions as an inhibitory site of prolactin gene expression in nonpituitary cells and which was used to clone Cart-1. 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.
Protein involved in the transfer of genetic information from DNA to messenger RNA (mRNA) by DNA-directed RNA polymerase. In the case of some RNA viruses, protein involved in the transfer of genetic information from RNA to messenger RNA (mRNA) by RNA-directed RNA polymerase.
Protein involved in development, the process whereby a multicellular organism develops from its early immature forms, e.g., zygote, larva, embryo, into an adult.
A reference proteome is a set of protein sequences derived from a complete proteome which constitutes a defined standard for a particular user community. Reference proteomes are manually defined according to a number of criteria. They cover the proteomes of well- studied model organisms and other proteomes of interest for biomedical and biotechnological research. Reference proteomes have been selected to provide broad coverage of the tree of life, and constitute a representative cross-section of the taxonomic diversity to be found within UniProtKB.