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Runx2

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Title: Runx2  
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Subject: Core binding factor, RUNX3, ATF4, RUNX1, C-jun
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Runx2

Runt-related transcription factor 2
PDB rendering based on 1cmo.
Available structures
PDB Ortholog search: PDBe, RCSB
Identifiers
Symbols  ; AML3; CBF-alpha-1; CBFA1; CCD; CCD1; CLCD; OSF-2; OSF2; PEA2aA; PEBP2aA
External IDs GeneCards:
RNA expression pattern
Orthologs
Species Human Mouse
Entrez
Ensembl
UniProt
RefSeq (mRNA)
RefSeq (protein)
Location (UCSC)
PubMed search

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.

Contents

  • Function 1
  • Pathology 2
  • Co-factors 3
  • Interactions 4
  • See also 5
  • References 6
  • Further reading 7
  • External links 8

Function

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

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

Co-factors

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

RUNX2 has been shown to interact with:

miR-133 directly inhibits Runx2.[14]

See also

References

  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.  
  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.  
  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.  
  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.  
  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.  
  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.  
  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.  
  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.  
  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.  
  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.  
  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.  
  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.  
  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.  

Further reading

  • Otto F, Kanegane H, Mundlos S (2002). "Mutations in the RUNX2 gene in patients with cleidocranial dysplasia.". Hum. Mutat. 19 (3): 209–16.  
  • Komori T (2002). "[Cbfa1/Runx2, an essential transcription factor for the regulation of osteoblast differentiation]". Nippon Rinsho. 60 Suppl 3: 91–7.  
  • Stock M, Otto F (2005). "Control of RUNX2 isoform expression: the role of promoters and enhancers.". J. Cell. Biochem. 95 (3): 506–17.  
  • Blyth K, Cameron ER, Neil JC (2005). "The RUNX genes: gain or loss of function in cancer.". Nat. Rev. Cancer 5 (5): 376–87.  
  • 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.  
  • 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.  

External links

  • GeneReviews/NCBI/NIH/UW entry on Cleidocranial Dysplasia
  • Runx2 protein at the US National Library of Medicine Medical Subject Headings (MeSH)
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