RUNX3 Human
Description
Definition and Gene Overview
The RUNX3 gene is located on human chromosome 1p36.1 and encodes a 415-amino acid protein (Fig. 1). It shares structural homology with RUNX1 and RUNX2, forming heterodimers with core-binding factor beta (CBFβ) to bind DNA motifs (5'-YGYGGT-3') and regulate transcription .
Key Features
Gene Structure and Regulation
The RUNX3 gene spans ~65 kb, with conserved CpG islands and two promoter regions (P1 and P2) that drive cell-type-specific expression .
Genomic Organization
Regulation:
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Epigenetic Silencing: Hypoxia induces G9a-mediated methylation of RUNX3, promoting cancer cell proliferation by suppressing immune response .
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Post-Translational Modifications: Acetylation by p300 enhances interaction with BRD2, transiently inducing cell cycle inhibitors (e.g., CDKN1A) .
Hematopoiesis
RUNX3 regulates myeloid lineage commitment and suppresses granulopoiesis:
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Overexpression in AML: Associated with reduced granulocyte differentiation and poor survival .
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Aging: Declining RUNX3 levels correlate with impaired erythropoiesis and anemia in the elderly .
Experimental Evidence
| Study | Key Findings |
|---|---|
| RUNX3 Overexpression | Reduced CD11b/CD15 expression, impaired granulocyte maturation |
| RUNX3 Knockdown | Minimal impact on myeloid development due to redundancy with RUNX1 |
Immune Regulation
RUNX3 modulates immune cell differentiation and function:
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T Regulatory Cells (Tregs): Induced by TGF-β, RUNX3 binds to FOXP3 promoters, enhancing Treg suppressive capacity .
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Natural Killer (NK) Cells: Directly activates NCR1 (NKp46), a key activating receptor, via RUNX binding motifs .
Mechanistic Insights
AML Subtype Analysis
| Subtype | RUNX3 Expression | Outcome |
|---|---|---|
| CBF AML (inv(16)/t(8;21)) | Low | Favorable prognosis |
| Non-CBF AML | High (26%) | Adverse prognosis |
Aging and Hematopoietic Decline
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Erythroid Dysfunction: Reduced RUNX3 in aged HSCs impairs KLF1 and GATA1 expression, leading to anemia .
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Lineage Skewing: RUNX3 decline favors granulopoiesis over lymphopoiesis, contributing to immune senescence .
Research Highlights
Product Specs
Product Science Overview
RUNX3 is characterized by the presence of a Runt domain (amino acids 54-186), which is essential for DNA binding. Additionally, it contains a proline/serine/threonine-rich region (amino acids 191-415) that is involved in the transcriptional activation of target genes . RUNX3 forms dimers with the core-binding factor beta (CBF-beta), which enhances its DNA-binding affinity and stability .
RUNX3 is involved in several critical biological processes:
- Growth Control of Gastric Epithelium: RUNX3 is necessary for the regulation of cell growth in the gastric epithelium. It acts as a tumor suppressor in gastric cancer by inhibiting the proliferation of gastric epithelial cells .
- Neurogenesis of Dorsal Root Ganglia: RUNX3 plays a vital role in the development of the nervous system, particularly in the neurogenesis of dorsal root ganglia .
- T Cell Differentiation: RUNX3 is essential for the differentiation of T cells, which are crucial components of the immune system .
RUNX3 has been implicated in various cancers and other diseases:
- Tumor Suppression: RUNX3 acts as a tumor suppressor in several types of cancers, including gastric cancer, colon cancer, and lung cancer. Its expression is often silenced in tumors due to promoter hypermethylation, loss of heterozygosity, or histone modifications .
- Acute Myeloid Leukemia (AML): RUNX3 is also known as AML2 due to its involvement in acute myeloid leukemia. It plays a role in the regulation of hematopoiesis and is frequently mutated in AML .
Recombinant RUNX3 is produced using various expression systems, such as E. coli. The recombinant protein is typically tagged with a His-tag for purification purposes and is available in lyophilized form for research use . It is used in various research applications to study its function and role in different biological processes and diseases.
