CBF binds to the core site, 5'-PYGPYGGT-3', of a number of enhancers and promoters, including murine leukemia virus, polyomavirus enhancer, T-cell receptor enhancers, lck, IL-3 and GM-CSF promoters.
cDNAs corresponding to three human runt domain containing genes, AML1, AML2, and AML3, were isolated and characterized. In addition to homology in the highly conserved runt domain, extensive sequence similarities were also observed in other parts of the proteins. All three carried an identical, putative ATP binding site -GRSGRGKS-, and their C-terminal halves were particularly rich in proline and serine residues. While AML1 cDNAs were cloned by others, AML2 represents a new member, not previously described, of the runt domain gene family, and AML3 was identified as the human homologue of mouse PEB-P2 alpha A. The chromosomal location of AML1 to chromosome 21q22 was confirmed, while AML2 and AML3 were mapped to chromosome regions 1p36 and 6p21, respectively. Analysis of AML1 and AML2 expression in hematopoietic cell lines revealed a distinct pattern of expression.
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 InteractionUniProtKB
RUNX3 is a transcription factor that functions as a tumor suppressor. In some cancers, RUNX3 expression is down-regulated, usually due to promoter hypermethylation. Recently, it was found that RUNX3 can also be inactivated by the mislocalization of the protein in the cytoplasm. The molecular mechanisms controlling this mislocalization are poorly understood. In this study, we found that the overexpression of Src results in the tyrosine phosphorylation and cytoplasmic localization of RUNX3. We also found that the tyrosine residues of endogenous RUNX3 are phosphorylated and that the protein is localized in the cytoplasm in Src-activated cancer cell lines. We further showed that the knockdown of Src by small interfering RNA, or the inhibition of Src kinase activity by a chemical inhibitor, causes the re-localization of RUNX3 to the nucleus. Collectively, our results demonstrate that the tyrosine phosphorylation of RUNX3 by activated Src is associated with the cytoplasmic localization of RUNX3 in gastric and breast cancers.
Evidence
2:
Inferred from Physical InteractionIntAct
Proc. Natl. Acad. Sci. U.S.A. 95, 11590-11595 (1998)[PubMed:9751710]
The mammalian AML/CBFalpha runt domain (RD) transcription factors regulate hematopoiesis and osteoblast differentiation. Like their Drosophila counterparts, most mammalian RD proteins terminate in a common pentapeptide, VWRPY, which serves to recruit the corepressor Groucho (Gro). Using a yeast two-hybrid assay, in vitro association and pull-down experiments, we demonstrate that Gro and its mammalian homolog TLE1 specifically interact with AML1 and AML2. In addition to the VWRPY motif, other C-terminal sequences are required for these interactions with Gro/TLE1. TLE1 inhibits AML1-dependent transactivation of the T cell receptor (TCR) enhancers alpha and beta, which contain functional AML binding sites, in transfected Jurkat T cells. LEF-1 is an additional transcription factor that mediates transactivation of TCR enhancers. LEF-1 and its Drosophila homolog Pangolin (Pan) are involved in the Wnt/Wg signaling pathway through interactions with the coactivator beta-catenin and its highly conserved fly homolog Armadillo (Arm). We show that TLE/Gro interacts with LEF-1 and Pan, and inhibits LEF-1:beta-catenin-dependent transcription. These data indicate that, in addition to their activity as transcriptional activators, AML1 and LEF-1 can act, through recruitment of the corepressor TLE1, as transcriptional repressors in TCR regulation and Wnt/Wg signaling.
Evidence
3:
Inferred from Physical InteractionIntAct
In intestinal epithelial cells, inactivation of APC, a key regulator of the Wnt pathway, activates beta-catenin to initiate tumorigenesis. However, other alterations may be involved in intestinal tumorigenesis. Here we found that RUNX3, a gastric tumor suppressor, forms a ternary complex with beta-catenin/TCF4 and attenuates Wnt signaling activity. A significant fraction of human sporadic colorectal adenomas and Runx3(+/-) mouse intestinal adenomas showed inactivation of RUNX3 without apparent beta-catenin accumulation, indicating that RUNX3 inactivation independently induces intestinal adenomas. In human colon cancers, RUNX3 is frequently inactivated with concomitant beta-catenin accumulation, suggesting that adenomas induced by inactivation of RUNX3 may progress to malignancy. Taken together, these data demonstrate that RUNX3 functions as a tumor suppressor by attenuating Wnt signaling.
Interacting selectively and non-covalently with a specific sequence of DNA that is part of a regulatory region that controls the transcription of a gene or cistron by RNA polymerase II.
ISSOrtholog Curator
Sequence-specific DNA binding RNA polymerase II transcription factor activitydefinition[GO:0000981]
Interacting selectively and non-covalently with a specific DNA sequence in order to modulate transcription by RNA polymerase II. The transcription factor may or may not also interact selectively with a protein or macromolecular complex.
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.
Core binding factor (CBF) is a heterodimeric transcription factor composed of two distinct subunits. The monomeric beta subunit is ubiquitously expressed, whereas expression of the three alpha subunits isolated previously seems to be restricted mainly to hematopoietic tissues. To isolate additional alpha genes, degenerate oligonucleotides derived from the runt domain--a region shared by all alpha genes--were used for screening cDNA libraries. A 228-bp fragment was isolated from a mouse thymus cDNA library, which showed 82 and 76% DNA sequence identity to the previously isolated murine alpha genes, Cbfa1 and Cbfa2. This novel alpha gene was named Cbfa3. The corresponding sequence from the human homolog CBFA3 was obtained by cosmid cloning and sequencing of the appropriate restriction fragment. The corresponding regions of mouse Cbfa3 and human CBFA3 show 91% nucleotide identity and 100% protein identity. In situ hybridization and physical mapping of somatic cell hybrids localized CBFA3 to chromosome 1p35-pter.
The chemotaxis process that directs the migration of an axon growth cone to a specific target site in response to a combination of attractive and repulsive cues.
The appearance of interferon-gamma due to biosynthesis or secretion following a cellular stimulus, resulting in an increase in its intracellular or extracellular levels. Interferon-gamma is also known as type II interferon.
The process whose specific outcome is the progression of a neuron whose cell body is located in the peripheral nervous system, from initial commitment of the cell to a neuronal fate, to the fully functional differentiated neuron.
The transcription factor Brn3a, product of the pou4f1 gene, is expressed in most sensory neurons throughout embryogenesis. Prior work has demonstrated a role for Brn3a in the repression of early neurogenic genes; here we describe a second major role for Brn3a in the specification of sensory subtypes in the trigeminal ganglion (TG). Sensory neurons initially co-express multiple Trk-family neurotrophin receptors, but are later marked by the unique expression of TrkA, TrkB or TrkC. Maturation of these sensory subtypes is known to depend on the expression of Runx transcription factors. Newborn Brn3a knockout mice fail to express TrkC, which is associated in the TG with mechanoreceptors, plus a set of functional genes associated with nociceptor subtypes. In embryonic Brn3a-/- ganglia, the normal expression of Runx3 is never initiated in TrkC+ neurons, and Runx1 expression is greatly attenuated in TrkA+ nociceptors. These changes are accompanied by expanded expression of TrkB in neurons that abnormally express multiple Trks, followed by the loss of TrkC and TrkA expression. In transgenic embryos expressing a Brn3a-VP16 dominant transactivator, Runx3 mRNA expression is increased, suggesting that it is a direct regulatory target of Brn3a. Chromatin immunoprecipitation confirms that Brn3a binds in vivo to a conserved upstream enhancer element within histone H3-acetylated chromatin in the Runx3 locus. Together these data show that Brn3a acts upstream of the Runx factors, which then repress TrkB expression to allow establishment of the non-overlapping Trk receptor profiles and correct terminally differentiated phenotypes.
RUNX3 is a transcription factor that functions as a tumor suppressor. In some cancers, RUNX3 expression is down-regulated, usually due to promoter hypermethylation. Recently, it was found that RUNX3 can also be inactivated by the mislocalization of the protein in the cytoplasm. The molecular mechanisms controlling this mislocalization are poorly understood. In this study, we found that the overexpression of Src results in the tyrosine phosphorylation and cytoplasmic localization of RUNX3. We also found that the tyrosine residues of endogenous RUNX3 are phosphorylated and that the protein is localized in the cytoplasm in Src-activated cancer cell lines. We further showed that the knockdown of Src by small interfering RNA, or the inhibition of Src kinase activity by a chemical inhibitor, causes the re-localization of RUNX3 to the nucleus. Collectively, our results demonstrate that the tyrosine phosphorylation of RUNX3 by activated Src is associated with the cytoplasmic localization of RUNX3 in gastric and breast cancers.
PEBP2/CBF is a heterodimeric transcription factor composed of alpha and beta subunits. Previously, we reported two distinct mouse genes, PEBP2 alpha A and PEBP2 alpha B, which encode the alpha subunit. PEBP2 alpha B is the homologue of human AML1, encoding the acute myeloid leukemia 1 protein. AML1 and human PEBP2/CBF beta were detected independently at the breakpoints of two characteristic chromosome translocations observed frequently in two subtypes of acute myeloid leukemia. The PEBP2 alpha proteins contain a 128-amino-acid (aa) region highly homologous to the Drosophila melanogaster segmentation gene runt. The evolutionarily conserved region, named the Runt domain, harbors DNA-binding and heterodimerizing activities. In this study, we identified the third Runt-domain-encoding gene, PEBP2 alpha C, which maps to 1p36.11-p36.13 in the human chromosome and encodes a 415-aa protein. PEBP2 alpha C forms a heterodimer with PEBP2 beta, binds to the PEBP2 site and transactivates transcription, similar to PEBP2 alpha A and PEBP2 alpha B.
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).
Core binding factor (CBF) is a heterodimeric transcription factor composed of two distinct subunits. The monomeric beta subunit is ubiquitously expressed, whereas expression of the three alpha subunits isolated previously seems to be restricted mainly to hematopoietic tissues. To isolate additional alpha genes, degenerate oligonucleotides derived from the runt domain--a region shared by all alpha genes--were used for screening cDNA libraries. A 228-bp fragment was isolated from a mouse thymus cDNA library, which showed 82 and 76% DNA sequence identity to the previously isolated murine alpha genes, Cbfa1 and Cbfa2. This novel alpha gene was named Cbfa3. The corresponding sequence from the human homolog CBFA3 was obtained by cosmid cloning and sequencing of the appropriate restriction fragment. The corresponding regions of mouse Cbfa3 and human CBFA3 show 91% nucleotide identity and 100% protein identity. In situ hybridization and physical mapping of somatic cell hybrids localized CBFA3 to chromosome 1p35-pter.
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.
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.
My favorites 
My labels 
Login
