RUNX3

RUNX3
Identifiers
Aliases	RUNX3, AML2, CBFA3, PEBP2aC, runt related transcription factor 3, RUNX family transcription factor 3
External IDs	OMIM: 600210 MGI: 102672 HomoloGene: 37914 GeneCards: RUNX3
Gene location (Human)
Chr.	Chromosome 1 (human)[1]
End	24,965,121 bp[1]
Gene location (Mouse)
Chr.	Chromosome 4 (mouse)[2]
End	135,177,990 bp[2]
RNA expression pattern
	; ;
	More reference expression data
Gene ontology
Molecular function	• DNA binding; • RNA polymerase II regulatory region sequence-specific DNA binding; • GO:0001131, GO:0001151, GO:0001130, GO:0001204 DNA-binding transcription factor activity; • GO:0001948 protein binding; • ATP binding; • GO:0001200, GO:0001133, GO:0001201 DNA-binding transcription factor activity, RNA polymerase II-specific;
Cellular component	• cytoplasm; • nuclear chromatin; • cell nucleus; • nucleolus; • intracellular membrane-bounded organelle; • nucleoplasm; • cytosol; • core-binding factor complex;
Biological process	• peripheral nervous system neuron development; • regulation of transcription, DNA-templated; • chondrocyte differentiation; • ossification; • regulation of transcription from RNA polymerase II promoter; • negative regulation of cell cycle; • negative regulation of transcription from RNA polymerase II promoter; • transcription from RNA polymerase II promoter; • transcription, DNA-templated; • positive regulation of transcription, DNA-templated; • protein phosphorylation; • negative regulation of epithelial cell proliferation; • regulation of cell differentiation; • response to transforming growth factor beta; • haematopoiesis; • negative regulation of CD4-positive, alpha-beta T cell differentiation; • positive regulation of CD8-positive, alpha-beta T cell differentiation; • neuron differentiation;
	Sources:Amigo / QuickGO
Orthologs
	864
	12399
	ENSG00000020633
	ENSMUSG00000070691
	Q13761
	Q64131
	NM_001031680; NM_004350; NM_001320672
	NM_019732; NM_001369050
	NP_001026850; NP_001307601; NP_004341
	NP_062706; NP_001355979
	Wikidata
View/Edit Human	View/Edit Mouse

Runt-related transcription factor 3 is a protein that in humans is encoded by the RUNX3 gene.[5]

Function

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,[6] 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.[7]

In melanocytic cells RUNX3 gene expression may be regulated by MITF.[8]

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.[9]

The RUNX3 controversy

In 2011 serious doubt was cast over the tumor suppressor function of Runx3 originated from the earlier publication by Li and co-workers.[10] On the basis of the original study by Li and co-workers (2002), the majority of later literature citing Li and co-workers (2002) assumed that RUNX3 was expressed in the normal gut epithelium and that it is therefore likely to act as a tumor suppressor in the particular epithelial cancer investigated. Most of this literature used RUNX3 promoter methylation status in various cancers as a proxy for its expression. However, quite many genes are known to be methylated in tumor cell genomes, and the majority of these genes are not expressed in the normal tissue of origin of these cancers. Others used poorly characterized (or fully invalidated) antibodies to detect the RUNX3 protein, or used RT-PCR or validated antibodies and failed to detect RUNX3 in the gut epithelium but still did not question the original finding by Li and co-workers (2002). This facts have recently been discussed in a book by Ülo Maiväli.[11]

Interactions

RUNX3 has been shown to interact with TLE1.[12]

References

GRCh38: Ensembl release 89: ENSG00000020633 - Ensembl, May 2017
GRCm38: Ensembl release 89: ENSMUSG00000070691 - Ensembl, May 2017
"Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
"Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
Levanon D, Negreanu V, Bernstein Y, Bar-Am I, Avivi L, Groner Y (Sep 1994). "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 (Apr 1998). "Site-directed mutagenesis supports a three-dimensional model of the runt domain". Journal of Molecular Biology. 277 (3): 509–12. doi:10.1006/jmbi.1998.1633. PMID 9533875. S2CID 13139512.
"Entrez Gene: RUNX3 runt-related transcription factor 3".
Hoek KS, Schlegel NC, Eichhoff OM, Widmer DS, Praetorius C, Einarsson SO, Valgeirsdottir S, Bergsteinsdottir K, Schepsky A, Dummer R, Steingrimsson E (Dec 2008). "Novel MITF targets identified using a two-step DNA microarray strategy". Pigment Cell & Melanoma Research. 21 (6): 665–76. doi:10.1111/j.1755-148X.2008.00505.x. PMID 19067971.
Li QL, Ito K, Sakakura C, Fukamachi H, Inoue Ki, Chi XZ, Lee KY, Nomura S, Lee CW, Han SB, Kim HM, Kim WJ, Yamamoto H, Yamashita N, Yano T, Ikeda T, Itohara S, Inazawa J, Abe T, Hagiwara A, Yamagishi H, Ooe A, Kaneda A, Sugimura T, Ushijima T, Bae SC, Ito Y (Apr 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. S2CID 11362226.
Levanon D, Bernstein Y, Negreanu V, Bone KR, Pozner A, Eilam R, Lotem J, Brenner O, Groner Y (Oct 2011). "Absence of Runx3 expression in normal gastrointestinal epithelium calls into question its tumour suppressor function". EMBO Mol Med. 3 (10): 593–604. doi:10.1002/emmm.201100168. PMC 3258485. PMID 21786422.
Maiväli, Ülo (2015). Interpreting Biomedical Science. Academic Press. pp. 44–45. ISBN 9780124186897.
Levanon D, Goldstein RE, 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". Proceedings of the National Academy of Sciences of the United States of America. 95 (20): 11590–5. Bibcode:1998PNAS...9511590L. doi:10.1073/pnas.95.20.11590. PMC 21685. PMID 9751710.

External links

RUNX3+protein,+human at the US National Library of Medicine Medical Subject Headings (MeSH)

This article incorporates text from the United States National Library of Medicine, which is in the public domain.

This article is issued from Wikipedia. The text is licensed under Creative Commons - Attribution - Sharealike. Additional terms may apply for the media files.

[refGRCh38Ensembl-1] GRCh38: Ensembl release 89: ENSG00000020633 - Ensembl, May 2017

[refGRCm38Ensembl-2] GRCm38: Ensembl release 89: ENSMUSG00000070691 - Ensembl, May 2017

[3] "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.

[4] "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.

[5] Levanon D, Negreanu V, Bernstein Y, Bar-Am I, Avivi L, Groner Y (Sep 1994). "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.

[6] Levanon D, Eisenstein M, Groner Y (Apr 1998). "Site-directed mutagenesis supports a three-dimensional model of the runt domain". Journal of Molecular Biology. 277 (3): 509–12. doi:10.1006/jmbi.1998.1633. PMID 9533875. S2CID 13139512.

[entrez-7] "Entrez Gene: RUNX3 runt-related transcription factor 3".

[8] Hoek KS, Schlegel NC, Eichhoff OM, Widmer DS, Praetorius C, Einarsson SO, Valgeirsdottir S, Bergsteinsdottir K, Schepsky A, Dummer R, Steingrimsson E (Dec 2008). "Novel MITF targets identified using a two-step DNA microarray strategy". Pigment Cell & Melanoma Research. 21 (6): 665–76. doi:10.1111/j.1755-148X.2008.00505.x. PMID 19067971.

[9] Li QL, Ito K, Sakakura C, Fukamachi H, Inoue Ki, Chi XZ, Lee KY, Nomura S, Lee CW, Han SB, Kim HM, Kim WJ, Yamamoto H, Yamashita N, Yano T, Ikeda T, Itohara S, Inazawa J, Abe T, Hagiwara A, Yamagishi H, Ooe A, Kaneda A, Sugimura T, Ushijima T, Bae SC, Ito Y (Apr 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. S2CID 11362226.

[10] Levanon D, Bernstein Y, Negreanu V, Bone KR, Pozner A, Eilam R, Lotem J, Brenner O, Groner Y (Oct 2011). "Absence of Runx3 expression in normal gastrointestinal epithelium calls into question its tumour suppressor function". EMBO Mol Med. 3 (10): 593–604. doi:10.1002/emmm.201100168. PMC 3258485. PMID 21786422.

[11] Maiväli, Ülo (2015). Interpreting Biomedical Science. Academic Press. pp. 44–45. ISBN 9780124186897.

[12] Levanon D, Goldstein RE, 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". Proceedings of the National Academy of Sciences of the United States of America. 95 (20): 11590–5. Bibcode:1998PNAS...9511590L. doi:10.1073/pnas.95.20.11590. PMC 21685. PMID 9751710.