RUNX3

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RUNX3
Protein RUNX3 PDB 1cmo.png
Identifiers
AliasesRUNX3, AML2, CBFA3, PEBP2aC, runt related transcription factor 3, RUNX family transcription factor 3
External IDsOMIM: 600210 MGI: 102672 HomoloGene: 37914 GeneCards: RUNX3
Gene location (Human)
Chromosome 1 (human)
Chr.Chromosome 1 (human)[1]
Chromosome 1 (human)
Genomic location for RUNX3
Genomic location for RUNX3
Band1p36.11Start24,899,511 bp[1]
End24,965,121 bp[1]
RNA expression pattern
PBB GE RUNX3 204197 s at fs.png

PBB GE RUNX3 204198 s at fs.png
More reference expression data
Orthologs
SpeciesHumanMouse
Entrez
Ensembl
UniProt
RefSeq (mRNA)

NM_001031680
NM_004350
NM_001320672

NM_019732
NM_001369050

RefSeq (protein)

NP_001026850
NP_001307601
NP_004341

NP_062706
NP_001355979

Location (UCSC)Chr 1: 24.9 – 24.97 MbChr 4: 135.12 – 135.18 Mb
PubMed search[3][4]
Wikidata
View/Edit HumanView/Edit Mouse

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

Function[edit]

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[edit]

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[edit]

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 novel by Ülo Maiväli.[11]

Interactions[edit]

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

See also[edit]

References[edit]

  1. ^ a b c GRCh38: Ensembl release 89: ENSG00000020633 - Ensembl, May 2017
  2. ^ a b c 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.
  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.
  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. doi:10.1073/pnas.95.20.11590. PMC 21685. PMID 9751710.

Further reading[edit]

External links[edit]

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