| General information | Literature | Expression | Regulation | Mutation | Interaction |
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Basic Information |
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|---|---|
Gene ID | 860 |
Name | RUNX2 |
Synonymous | AML3|CBF-alpha-1|CBFA1|CCD|CCD1|CLCD|OSF-2|OSF2|PEA2aA|PEBP2aA;runt-related transcription factor 2;RUNX2;runt-related transcription factor 2 |
Definition | PEA2-alpha A|PEBP2-alpha A|SL3-3 enhancer factor 1 alpha A subunit|SL3/AKV core-binding factor alpha A subunit|acute myeloid leukemia 3 protein|core-binding factor, runt domain, alpha subunit 1|oncogene AML-3|osteoblast-specific transcription factor 2|pol |
Position | 6p21 |
Gene type | protein-coding |
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Title |
Abstract |
| Runx2 deficiency and defective subnuclear targeting bypass senescence to promote immortalization and tumorigenic potential. | The osteogenic Runt-related (Runx2) transcription factor negatively regulates proliferation and ribosomal gene expression in normal diploid osteoblasts, but is up-regulated in metastatic breast and prostate cancer cells. Thus, Runx2 may function as a tumor suppressor or an oncogene depending on the cellular context. Here we show that Runx2-deficient primary osteoblasts fail to undergo senescence as indicated by the absence of beta-gal activity and p16(INK4a) tumor suppressor expression. Primary Runx2-null osteoblasts have a growth advantage and exhibit loss of p21(WAF1/CIP1) and p19(ARF) expression. Reintroduction of WT Runx2, but not a subnuclear targeting-defective mutant, induces both p21(WAF/CIP1) and p19(ARF) mRNA and protein resulting in cell-cycle inhibition. Accumulation of spontaneous phospho-H2A.X foci, loss of telomere integrity and the Mre11/Rad50/Nbs1 DNA repair complex, and a delayed DNA repair response all indicate that Runx2 deficiency leads to genomic instability. We propose that Runx2 functions as a tumor suppressor in primary diploid osteoblasts and that subnuclear targeting contributes to Runx2-mediated tumor suppression. |