RUNX2

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Runt-related transcription factor 2
Protein RUNX2 PDB 1cmo.png
PDB rendering based on 1cmo.
Available structures
PDB Ortholog search: PDBe, RCSB
Identifiers
Symbols RUNX2 ; AML3; CBFA1; CCD; CCD1; CLCD; OSF-2; OSF2; PEA2aA; PEBP2A1; PEBP2A2; PEBP2aA; PEBP2aA1
External IDs OMIM600211 MGI99829 HomoloGene68389 GeneCards: RUNX2 Gene
RNA expression pattern
PBB GE RUNX2 216994 s at tn.png
PBB GE RUNX2 221282 x at tn.png
More reference expression data
Orthologs
Species Human Mouse
Entrez 860 12393
Ensembl ENSG00000124813 ENSMUSG00000039153
UniProt Q13950 Q08775
RefSeq (mRNA) NM_001015051 NM_001145920
RefSeq (protein) NP_001015051 NP_001139392
Location (UCSC) Chr 6:
45.3 – 45.63 Mb
Chr 17:
44.5 – 44.81 Mb
PubMed search [1] [2]

Runt-related transcription factor 2 (RUNX2) also known as core-binding factor subunit alpha-1 (CBF-alpha-1) is a protein that in humans is encoded by the RUNX2 gene. RUNX2 is a key transcription factor associated with osteoblast differentiation.

Function[edit]

This protein is a member of the RUNX family of transcription factors and has a Runt DNA-binding domain. It is essential for osteoblastic differentiation and skeletal morphogenesis and acts as a scaffold for nucleic acids and regulatory factors involved in skeletal gene expression. The protein can bind DNA both as a monomer or, with more affinity, as a subunit of a heterodimeric complex. Transcript variants of the gene that encode different protein isoforms result from the use of alternate promoters as well as alternate splicing.[1]

Differences in RUNX2 are hypothesized to be the cause of the skeletal differences between modern humans and early humans such as Neanderthals. These differences include a different shape of the skull, a bell-shaped chest in Neanderthals, etc.[2]

The binding interactions of RUNX2 change as cells go through mitosis, with binding affinity increasing as chromosomes condense and then decreasing through subsequent mitotic phases. The increased residence of RUNX2 at mitotic chromosomes may reflect its epigenetic function in "bookmarking" of target genes in cancer cells.[3]

Pathology[edit]

Mutations in Cbfa1/Runx2 are associated with the disease Cleidocranial dysostosis.

Co-factors[edit]

Runx proteins represent the alpha DNA binding subunit of a heteromeric protein complex that also includes the non-DNA binding beta-subunit which increases the DNA binding affinity of the alpha subunit. In addition, there is a large cohort of regulatory proteins that bind to the C-terminus of Runx2 to modify its transcriptional function. [4]

Interactions[edit]

RUNX2 has been shown to interact with:

miR-133 directly inhibits Runx2.[14]

See also[edit]

References[edit]

  1. ^ "Entrez Gene: RUNX2 runt-related transcription factor 2". 
  2. ^ Green RE, Krause J, Briggs AW, et al. (May 2010). "A draft sequence of the Neandertal genome". Science 328 (5979): 710–22. doi:10.1126/science.1188021. PMID 20448178. 
  3. ^ Pockwinse SM, Kota KP, Quaresma AJ, et al. (May 2011). "Live cell imaging of the cancer-related transcription factor RUNX2 during mitotic progression". Journal of Cellular Physiology 227 (1): 710–22. doi:10.1002/jcp.22465. PMID 20945391. 
  4. ^ Lian, JB; Javed, A, Zaidi, SK, Lengner, C, Montecino, M, van Wijnen, AJ, Stein, JL, Stein, GS (2004). "Regulatory controls for osteoblast growth and differentiation: role of Runx/Cbfa/AML factors.". Critical reviews in eukaryotic gene expression 14 (1-2): 1–41. PMID 15104525. 
  5. ^ Baniwal SK, Khalid O, Sir D, Buchanan G, Coetzee GA, Frenkel B (August 2009). "Repression of Runx2 by androgen receptor (AR) in osteoblasts and prostate cancer cells: AR binds Runx2 and abrogates its recruitment to DNA". Mol. Endocrinol. 23 (8): 1203–14. doi:10.1210/me.2008-0470. PMC 2718746. PMID 19389811. 
  6. ^ Khalid O, Baniwal SK, Purcell DJ, Leclerc N, Gabet Y, Stallcup MR, Coetzee GA, Frenkel B (December 2008). "Modulation of Runx2 activity by estrogen receptor-alpha: implications for osteoporosis and breast cancer". Endocrinology 149 (12): 5984–95. doi:10.1210/en.2008-0680. PMC 2613062. PMID 18755791. 
  7. ^ a b Hess J, Porte D, Munz C, Angel P (June 2001). "AP-1 and Cbfa/runt physically interact and regulate parathyroid hormone-dependent MMP13 expression in osteoblasts through a new osteoblast-specific element 2/AP-1 composite element". J. Biol. Chem. 276 (23): 20029–38. doi:10.1074/jbc.M010601200. PMID 11274169. 
  8. ^ a b D'Alonzo RC, Selvamurugan N, Karsenty G, Partridge NC (January 2002). "Physical interaction of the activator protein-1 factors c-Fos and c-Jun with Cbfa1 for collagenase-3 promoter activation". J. Biol. Chem. 277 (1): 816–22. doi:10.1074/jbc.M107082200. PMID 11641401. 
  9. ^ Schroeder TM, Kahler RA, Li X, Westendorf JJ (October 2004). "Histone deacetylase 3 interacts with runx2 to repress the osteocalcin promoter and regulate osteoblast differentiation". J. Biol. Chem. 279 (40): 41998–2007. doi:10.1074/jbc.M403702200. PMID 15292260. 
  10. ^ Pelletier N, Champagne N, Stifani S, Yang XJ (April 2002). "MOZ and MORF histone acetyltransferases interact with the Runt-domain transcription factor Runx2". Oncogene 21 (17): 2729–40. doi:10.1038/sj.onc.1205367. PMID 11965546. 
  11. ^ a b Zhang YW, Yasui N, Ito K, Huang G, Fujii M, Hanai J, Nogami H, Ochi T, Miyazono K, Ito Y (September 2000). "A RUNX2/PEBP2alpha A/CBFA1 mutation displaying impaired transactivation and Smad interaction in cleidocranial dysplasia". Proc. Natl. Acad. Sci. U.S.A. 97 (19): 10549–54. doi:10.1073/pnas.180309597. PMC 27062. PMID 10962029. 
  12. ^ a b Hanai J, Chen LF, Kanno T, Ohtani-Fujita N, Kim WY, Guo WH, Imamura T, Ishidou Y, Fukuchi M, Shi MJ, Stavnezer J, Kawabata M, Miyazono K, Ito Y (October 1999). "Interaction and functional cooperation of PEBP2/CBF with Smads. Synergistic induction of the immunoglobulin germline Calpha promoter". J. Biol. Chem. 274 (44): 31577–82. doi:10.1074/jbc.274.44.31577. PMID 10531362. 
  13. ^ Li X, Huang M, Zheng H, Wang Y, Ren F, Shang Y, Zhai Y, Irwin DM, Shi Y, Chen D, Chang Z (June 2008). "CHIP promotes Runx2 degradation and negatively regulates osteoblast differentiation". J. Cell Biol. 181 (6): 959–72. doi:10.1083/jcb.200711044. PMC 2426947. PMID 18541707. 
  14. ^ Li Z, Hassan MQ, Volinia S, van Wijnen AJ, Stein JL, Croce CM, Lian JB, Stein GS (September 2008). "A microRNA signature for a BMP2-induced osteoblast lineage commitment program". Proc. Natl. Acad. Sci. U.S.A. 105 (37): 13906–11. doi:10.1073/pnas.0804438105. PMC 2544552. PMID 18784367. 

Further reading[edit]

  • Otto F, Kanegane H, Mundlos S (2002). "Mutations in the RUNX2 gene in patients with cleidocranial dysplasia.". Hum. Mutat. 19 (3): 209–16. doi:10.1002/humu.10043. PMID 11857736. 
  • Komori T (2002). "[Cbfa1/Runx2, an essential transcription factor for the regulation of osteoblast differentiation]". Nippon Rinsho. 60 Suppl 3: 91–7. PMID 11979975. 
  • Stock M, Otto F (2005). "Control of RUNX2 isoform expression: the role of promoters and enhancers.". J. Cell. Biochem. 95 (3): 506–17. doi:10.1002/jcb.20471. PMID 15838892. 
  • Blyth K, Cameron ER, Neil JC (2005). "The RUNX genes: gain or loss of function in cancer.". Nat. Rev. Cancer 5 (5): 376–87. doi:10.1038/nrc1607. PMID 15864279. 
  • Schroeder TM, Jensen ED, Westendorf JJ (2005). "Runx2: a master organizer of gene transcription in developing and maturing osteoblasts.". Birth Defects Res. C Embryo Today 75 (3): 213–25. doi:10.1002/bdrc.20043. PMID 16187316. 
  • Frenkel B, Hong A, Baniwal SK, Coetzee GA, Ohlsson C, Khalid O, Gabet Y (August 2010). "Regulation of adult bone turnover by sex steroids". J. Cell. Physiol. 224 (2): 305–10. doi:10.1002/jcp.22159. PMID 20432458. 

External links[edit]