RUNX3

Runt-related transcription factor 3
	; PDB rendering based on 1cmo.
Available structures
PDB	1cmo, 1co1, 1e50, 1ean, 1eao, 1eaq, 1h9d, 1hjb, 1hjc, 1io4, 1ljm
Identifiers
Symbols	RUNX3; AML2; CBFA3; FLJ34510; MGC16070; PEBP2aC
External IDs	OMIM: 600210 MGI: 102672 HomoloGene: 37914 GeneCards: RUNX3 Gene
Gene Ontology
Molecular function	• DNA binding; • sequence-specific DNA binding transcription factor activity; • protein binding; • ATP binding;
Cellular component	• nucleus; • nucleus; • cytoplasm;
Biological process	• regulation of transcription, DNA-dependent; • regulation of transcription, DNA-dependent; • transcription from RNA polymerase II promoter; • protein phosphorylation; • induction of apoptosis; • cell proliferation; • negative regulation of cell cycle; • negative regulation of epithelial cell proliferation;
	Sources: Amigo / QuickGO
RNA expression pattern
	More reference expression data
Orthologs

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Runt-related transcription factor 3 is a protein that in humans is encoded by the RUNX3 gene.^[1]

This gene encodes a member of the runt domain-containing family of transcription factors. A heterodimer of this protein and a beta subunit forms a complex that binds to the core DNA sequence 5'-YGYGGT-3' found in a number of enhancers and promoters^[2], and can either activate or suppress transcription. It also interacts with other transcription factors. It functions as a tumor suppressor, and the gene is frequently deleted or transcriptionally silenced in cancer. Multiple transcript variants encoding different isoforms have been found for this gene.^[3]

In melanocytic cells RUNX3 gene expression may be regulated by MITF.^[4]

[edit] Knockout mouse

Runx3 null mouse gastric mucosa exhibits hyperplasia due to stimulated proliferation and suppressed apoptosis in epithelial cells, and the cells are resistant to TGF-beta stimulation.^[5]

[edit] Interactions

RUNX3 has been shown to interact with TLE1.^[6]

[edit] See also

[edit] References

^ Levanon D, Negreanu V, Bernstein Y, Bar-Am I, Avivi L, Groner Y (February 1995). "AML1, AML2, and AML3, the human members of the runt domain gene-family: cDNA structure, expression, and chromosomal localization". Genomics 23 (2): 425–32. doi:10.1006/geno.1994.1519. PMID 7835892.
^ Levanon D, Eisenstein M, Groner Y (April 1998). "Site-directed mutagenesis supports a three-dimensional model of the runt domain.". J Mol Biol. 277 (3): 509–12. doi:10.1006/jmbi.1998.1633. PMID 9533875. http://linkinghub.elsevier.com/retrieve/pii/S0022-2836(98)91633-3.
^ "Entrez Gene: RUNX3 runt-related transcription factor 3". http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=864.
^ Hoek KS, Schlegel NC, Eichhoff OM, et al. (2008). "Novel MITF targets identified using a two-step DNA microarray strategy". Pigment Cell Melanoma Res. 21 (6): 665–76. doi:10.1111/j.1755-148X.2008.00505.x. PMID 19067971.
^ Li QL, Ito K, Sakakura C, et al. (April 2002). "Causal relationship between the loss of RUNX3 expression and gastric cancer". Cell 109 (1): 113–24. doi:10.1016/S0092-8674(02)00690-6. PMID 11955451. http://linkinghub.elsevier.com/retrieve/pii/S0092867402006906.
^ Levanon, D; Goldstein R E, Bernstein Y, Tang H, Goldenberg D, Stifani S, Paroush Z, Groner Y (Sep. 1998). "Transcriptional repression by AML1 and LEF-1 is mediated by the TLE/Groucho corepressors". Proc. Natl. Acad. Sci. U.S.A. 95 (20): 11590–5. doi:10.1073/pnas.95.20.11590. PMC 21685. PMID 9751710. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=21685.

[edit] Further reading

Vogiatzi P, De Falco G, Claudio PP, Giordano A (2007). "How does the human RUNX3 gene induce apoptosis in gastric cancer? Latest data, reflections and reactions.". Cancer Biol. Ther. 5 (4): 371–4. PMID 16627973.
Wijmenga C, Speck NA, Dracopoli NC, et al. (1995). "Identification of a new murine runt domain-containing gene, Cbfa3, and localization of the human homolog, CBFA3, to chromosome 1p35-pter.". Genomics 26 (3): 611–4. doi:10.1016/0888-7543(95)80185-O. PMID 7607690.
Bae SC, Takahashi E, Zhang YW, et al. (1995). "Cloning, mapping and expression of PEBP2 alpha C, a third gene encoding the mammalian Runt domain.". Gene 159 (2): 245–8. doi:10.1016/0378-1119(95)00060-J. PMID 7622058.
Bae SC, Yamaguchi-Iwai Y, Ogawa E, et al. (1993). "Isolation of PEBP2 alpha B cDNA representing the mouse homolog of human acute myeloid leukemia gene, AML1.". Oncogene 8 (3): 809–14. PMID 8437866.
Levanon D, Goldstein RE, Bernstein Y, et al. (1998). "Transcriptional repression by AML1 and LEF-1 is mediated by the TLE/Groucho corepressors.". Proc. Natl. Acad. Sci. U.S.A. 95 (20): 11590–5. doi:10.1073/pnas.95.20.11590. PMC 21685. PMID 9751710. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=21685.
Bangsow C, Rubins N, Glusman G, et al. (2002). "The RUNX3 gene--sequence, structure and regulated expression.". Gene 279 (2): 221–32. doi:10.1016/S0378-1119(01)00760-0. PMID 11733147.
Li QL, Ito K, Sakakura C, et al. (2002). "Causal relationship between the loss of RUNX3 expression and gastric cancer.". Cell 109 (1): 113–24. doi:10.1016/S0092-8674(02)00690-6. PMID 11955451.
Strausberg RL, Feingold EA, Grouse LH, et al. (2003). "Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences.". Proc. Natl. Acad. Sci. U.S.A. 99 (26): 16899–903. doi:10.1073/pnas.242603899. PMC 139241. PMID 12477932. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=139241.
Waki T, Tamura G, Sato M, et al. (2003). "Promoter methylation status of DAP-kinase and RUNX3 genes in neoplastic and non-neoplastic gastric epithelia.". Cancer Sci. 94 (4): 360–4. doi:10.1111/j.1349-7006.2003.tb01447.x. PMID 12824905.
Puig-Kröger A, Sanchez-Elsner T, Ruiz N, et al. (2004). "RUNX/AML and C/EBP factors regulate CD11a integrin expression in myeloid cells through overlapping regulatory elements.". Blood 102 (9): 3252–61. doi:10.1182/blood-2003-02-0618. PMID 12855590.
Kato N, Tamura G, Fukase M, et al. (2003). "Hypermethylation of the RUNX3 gene promoter in testicular yolk sac tumor of infants.". Am. J. Pathol. 163 (2): 387–91. doi:10.1016/S0002-9440(10)63668-1. PMC 1868235. PMID 12875960. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=1868235.
Yang N, Zhang L, Zhang Y, Kazazian HH (2004). "An important role for RUNX3 in human L1 transcription and retrotransposition". Nucleic Acids Res. 31 (16): 4929–40. doi:10.1093/nar/gkg663. PMC 169909. PMID 12907736. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=169909.
Ota T, Suzuki Y, Nishikawa T, et al. (2004). "Complete sequencing and characterization of 21,243 full-length human cDNAs". Nat. Genet. 36 (1): 40–5. doi:10.1038/ng1285. PMID 14702039.
Li QL, Kim HR, Kim WJ, et al. (2004). "Transcriptional silencing of the RUNX3 gene by CpG hypermethylation is associated with lung cancer". Biochem. Biophys. Res. Commun. 314 (1): 223–8. doi:10.1016/j.bbrc.2003.12.079. PMID 14715269.
Xiao WH, Liu WW (2004). "Hemizygous deletion and hypermethylation of RUNX3 gene in hepatocellular carcinoma". World J. Gastroenterol. 10 (3): 376–80. PMID 14760761.
Oshimo Y, Oue N, Mitani Y, et al. (2004). "Frequent loss of RUNX3 expression by promoter hypermethylation in gastric carcinoma". Pathobiology 71 (3): 137–43. doi:10.1159/000076468. PMID 15051926.
Jin YH, Jeon EJ, Li QL, et al. (2004). "Transforming growth factor-beta stimulates p300-dependent RUNX3 acetylation, which inhibits ubiquitination-mediated degradation". J. Biol. Chem. 279 (28): 29409–17. doi:10.1074/jbc.M313120200. PMID 15138260.
Ku JL, Kang SB, Shin YK, et al. (2004). "Promoter hypermethylation downregulates RUNX3 gene expression in colorectal cancer cell lines". Oncogene 23 (40): 6736–42. doi:10.1038/sj.onc.1207731. PMID 15273736.
Sakakura C, Hagiwara A, Miyagawa K, et al. (2005). "Frequent downregulation of the runt domain transcription factors RUNX1, RUNX3 and their cofactor CBFB in gastric cancer". Int. J. Cancer 113 (2): 221–8. doi:10.1002/ijc.20551. PMID 15386419.