Runt-related transcription factor 3 is a

protein Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residues. Proteins perform a vast array of functions within organisms, including catalysing metabolic reactions, DNA replication, respo ...

that in humans is encoded by the ''RUNX3''

gene In biology, the word gene (from , ; "...Wilhelm Johannsen coined the word gene to describe the Mendelian units of heredity..." meaning ''generation'' or ''birth'' or ''gender'') can have several different meanings. The Mendelian gene is a ba ...

Function

This gene encodes a member of the

runt domain The Runt domain is an evolutionary conserved protein domain. The AML1/RUNX1 gene is rearranged by the t(8;21) translocation in acute myeloid leukemia. The gene is highly similar to the ''Drosophila melanogaster'' segmentation gene runt a ...

-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, 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. In melanocytic cells RUNX3 gene expression may be regulated by

MITF Microphthalmia-associated transcription factor also known as class E basic helix-loop-helix protein 32 or bHLHe32 is a protein that in humans is encoded by the ''MITF'' gene. MITF is a basic helix-loop-helix leucine zipper transcription factor ...

Knockout mouse

Runx3 null mouse gastric mucosa exhibits hyperplasia due to stimulated proliferation and suppressed

apoptosis Apoptosis (from grc, ἀπόπτωσις, apóptōsis, 'falling off') is a form of programmed cell death that occurs in multicellular organisms. Biochemical events lead to characteristic cell changes (morphology) and death. These changes incl ...

in epithelial cells, and the cells are resistant to TGF-beta stimulation.

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. 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.

Interactions

RUNX3 has been shown to

interact Advocates for Informed Choice, dba interACT or interACT Advocates for Intersex Youth, is a 501(c)(3) nonprofit organization using innovative strategies to advocate for the legal and human rights of children with intersex traits. The organizati ...

with

TLE1 Transducin-like enhancer protein 1 is a protein that in humans is encoded by the ''TLE1'' gene. Interactions TLE1 has been shown to interact Advocates for Informed Choice, doing business as, dba interACT or interACT Advocates for Intersex ...

References

External links

* {{NLM content Transcription factors