| Written | 2006-12 | Athanasios G Papavassiliou, Panos Ziros |
| Department of Biological Chemistry, Medical School, University of Athens, GR-11527 Goudi-Athens, Greece |
| Identity |
| Alias_names | CCD |
| CBFA1 | |
| CCD1 | |
| runt-related transcription factor 2 | |
| Alias_symbol (synonym) | AML3 |
| PEBP2A1 | |
| PEBP2aA1 | |
| Other alias | PEBP2-ALPHA-A |
| OSF2 | |
| HGNC (Hugo) | RUNX2 |
| LocusID (NCBI) | 860 |
| Atlas_Id | 42183 |
| Location | 6p21.1 [Link to chromosome band 6p21] |
| Location_base_pair | Starts at 45328317 and ends at 45551082 bp from pter ( according to hg19-Feb_2009) [Mapping RUNX2.png] |
| Fusion genes (updated 2016) | HS2ST1 (1p22.3) / RUNX2 (6p21.1) | MAX (14q23.3) / RUNX2 (6p21.1) | MDM2 (12q15) / RUNX2 (6p21.1) |
| RUNX2 (6p21.1) / IFT88 (13q12.11) | RUNX2 (6p21.1) / MAX (14q23.3) |
| DNA/RNA |
| Description | 124,63 kb, 8 Exon at least. |
| Transcription | The transcription of the RUNX2 gene is regulated by two different promoters. The larger P1 transcript gives rise to a protein starting with the amino acid sequence MASNS (Runx2-type II or OSF2/CBFA1a, 521 amino acids), whereas the P2 gives rise to a protein starting with MRIPV (Runx2-type I or isoform c, 507 amino acids). Transcript variants of this protein have been reported as well due to alternative splicing. |
| Protein |
| Description | Runx2 is a transcription factor belonging to Runx family. This family is characterized by a highly conserved region of 128 amino acids, termed the Runt domain. The Runt domain is responsible for DNA binding and heterodimerization with CBFB (PEBP2b), which increases its DNA-binding affinity and also stabilizes RUNX proteins against proteolytic degradation. The C-terminal portion is rich in proline, serine and threonine (PST region) and contains functional domains acting to regulate transcription. |
| Expression | Runx2 expression is largely restricted to osteoblasts and mesenchymal condensations forming bones, cartilages and teeth. |
| Localisation | Nuclear |
| Function | Runx2 is an osteoblast-specific transcription factor that plays a central role in osteoblast differentiation, chondrocyte maturation, bone formation and remodeling. Moreover, it is a key target of mechanical signals that affect bone biology. |
| Homology | RUNX family. |
| Mutations |
| Note | Heterozygous mutations (frameshift, nonsense, missense, splicing mutations) of the Runx2 gene have been identified in patients with Cleidocranial dysplasia (CCD). |
| Implicated in |
| Note | |
| Entity | Cleidocranial Dysplasia (CCD) |
| Disease | CCD is a dominantly inherited autosomal skeletal disorder that is characterized by open sutures and delayed closure of sutures, hypoplastic or aplastic clavicles, short stature, large fontanelles, dental anomalies and delayed skeletal development. |
| Prognosis | CCD does not affect life expectancy and most diagnosed persons enjoy good overall health. There is no specific treatment for CCD and the dental problems are the most significant complications. |
| Entity | Lymphomas |
| Disease | Runx2 and MYC collaborate in lymphoma development by suppressing apoptotic and growth arrest pathways in vivo. |
| Entity | Multiple myeloma. |
| Disease | Human myeloma cells express the bone regulating gene Runx2 and produce osteopontin that is involved in angiogenesis in multiple myeloma patients. |
| Entity | Metastatic properties of cancer cells. |
| Disease | Runx2 control multiple genes that contribute to the metastatic properties of cancer cells and their activity in the bone microenvironment. |
| Entity | Breast cancer. |
| Disease | Involvement of Runx2 transcription factors in breast cancer cells. |
| Entity | Malignant melanoma. |
| Disease | Coexpression of bone sialoprotein and Runx2, in malignant melanoma. |
| Entity | Prostate cancer. |
| Disease | Prostate cancer expression of runt-domain transcription factor Runx2. |
| Bibliography |
| Osteoblast-related transcription factors Runx2 (Cbfa1/AML3) and MSX2 mediate the expression of bone sialoprotein in human metastatic breast cancer cells. |
| Barnes GL, Javed A, Waller SM, Kamal MH, Hebert KE, Hassan MQ, Bellahcene A, Van Wijnen AJ, Young MF, Lian JB, Stein GS, Gerstenfeld LC |
| Cancer research. 2003 ; 63 (10) : 2631-2637. |
| PMID 12750290 |
| A natural history of cleidocranial dysplasia. |
| Cooper SC, Flaitz CM, Johnston DA, Lee B, Hecht JT |
| American journal of medical genetics. 2001 ; 104 (1) : 1-6. |
| PMID 11746020 |
| Osf2/Cbfa1: a transcriptional activator of osteoblast differentiation. |
| Ducy P, Zhang R, Geoffroy V, Ridall AL, Karsenty G |
| Cell. 1997 ; 89 (5) : 747-754. |
| PMID 9182762 |
| Genomic organization, expression of the human CBFA1 gene, and evidence for an alternative splicing event affecting protein function. |
| Geoffroy V, Corral DA, Zhou L, Lee B, Karsenty G |
| Mammalian genome : official journal of the International Mammalian Genome Society. 1998 ; 9 (1) : 54-57. |
| PMID 9434946 |
| Oncogenic potential of the RUNX gene family: 'overview'. |
| Ito Y |
| Oncogene. 2004 ; 23 (24) : 4198-4208. |
| PMID 15156173 |
| Impaired intranuclear trafficking of Runx2 (AML3/CBFA1) transcription factors in breast cancer cells inhibits osteolysis in vivo. |
| Javed A, Barnes GL, Pratap J, Antkowiak T, Gerstenfeld LC, van Wijnen AJ, Stein JL, Lian JB, Stein GS |
| Proceedings of the National Academy of Sciences of the United States of America. 2005 ; 102 (5) : 1454-1459. |
| PMID 15665096 |
| Targeted disruption of Cbfa1 results in a complete lack of bone formation owing to maturational arrest of osteoblasts. |
| Komori T, Yagi H, Nomura S, Yamaguchi A, Sasaki K, Deguchi K, Shimizu Y, Bronson RT, Gao YH, Inada M, Sato M, Okamoto R, Kitamura Y, Yoshiki S, Kishimoto T |
| Cell. 1997 ; 89 (5) : 755-764. |
| PMID 9182763 |
| Missense mutations abolishing DNA binding of the osteoblast-specific transcription factor OSF2/CBFA1 in cleidocranial dysplasia. |
| Lee B, Thirunavukkarasu K, Zhou L, Pastore L, Baldini A, Hecht J, Geoffroy V, Ducy P, Karsenty G |
| Nature genetics. 1997 ; 16 (3) : 307-310. |
| PMID 9207800 |
| RUNX: a trilogy of cancer genes. |
| Lund AH, van Lohuizen M |
| Cancer cell. 2002 ; 1 (3) : 213-215. |
| PMID 12086855 |
| Mutations involving the transcription factor CBFA1 cause cleidocranial dysplasia. |
| Mundlos S, Otto F, Mundlos C, Mulliken JB, Aylsworth AS, Albright S, Lindhout D, Cole WG, Henn W, Knoll JH, Owen MJ, Mertelsmann R, Zabel BU, Olsen BR |
| Cell. 1997 ; 89 (5) : 773-779. |
| PMID 9182765 |
| Cbfa1, a candidate gene for cleidocranial dysplasia syndrome, is essential for osteoblast differentiation and bone development. |
| Otto F, Thornell AP, Crompton T, Denzel A, Gilmour KC, Rosewell IR, Stamp GW, Beddington RS, Mundlos S, Olsen BR, Selby PB, Owen MJ |
| Cell. 1997 ; 89 (5) : 765-771. |
| PMID 9182764 |
| The bone-specific transcriptional regulator Cbfa1 is a target of mechanical signals in osteoblastic cells. |
| Ziros PG, Gil AP, Georgakopoulos T, Habeos I, Kletsas D, Basdra EK, Papavassiliou AG |
| The Journal of biological chemistry. 2002 ; 277 (26) : 23934-23941. |
| PMID 11960980 |
| Citation |
| This paper should be referenced as such : |
| Ziros, P ; Papavassiliou, AG |
| RUNX 2 (runt-related transcription factor 2) |
| Atlas Genet Cytogenet Oncol Haematol. 2007;11(2):109-110. |
| Free journal version : [ pdf ] [ DOI ] |
| On line version : http://AtlasGeneticsOncology.org/Genes/RUNX2ID42183ch6p21.html |
| Other Leukemias implicated (Data extracted from papers in the Atlas) [ 1 ] |
|
dic(9;18)(p13;q11) PAX5/ZNF521
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| External links |
| REVIEW articles | automatic search in PubMed |
| Last year publications | automatic search in PubMed |
| © Atlas of Genetics and Cytogenetics in Oncology and Haematology | indexed on : Fri Jun 30 11:17:29 CEST 2017 |
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