The cleidocranial dysplasia-related R131G mutation in the runt-related transcription factor RUNX2 disrupts binding to DNA but not CBF-β

Journal of Cellular Biochemistry

Volumn 110, Issue 1, 2010, Pages 97-103

  Han, Min Su ^a,b   Kim, Hyo Jin ^a,b   Wee, Hee Jun ^c   Lim, Kyung Eun ^a,b   Park, Na Rae ^a,b   Bae, Suk Chul ^c   Van Wijnen, Andre J ^d   Stein, Janet L ^d   Lian, Jane B ^d   Stein, Gary S ^d   Choi, Je Yong ^a,b  

^a Kyungpook National University School of Medicine   (South Korea)

^b Kyungpook National University   (South Korea)

^c Chungbuk National University   (South Korea)

^d UNIVERSITY OF MASSACHUSETTS MEDICAL SCHOOL   (United States)

Author keywords

Cleidocranial dysplasia (CCD); Core binding factor (CBF ); DNA binding activity; Heterodimerization; RUNX2; RUNX2R131G; Subcellular localization; Transactivation

Indexed keywords

ARGININE; CORE BINDING FACTOR BETA; GLYCINE; TRANSCRIPTION FACTOR RUNX2;

ANIMAL CELL; ARTICLE; CELL NUCLEUS; CELL STRAIN HEK293; CELLULAR DISTRIBUTION; CHO CELL; CLEIDOCRANIAL DYSPLASIA; CONTROLLED STUDY; HELA CELL; MISSENSE MUTATION; NONHUMAN; PRIORITY JOURNAL; PROTEIN DNA BINDING; PROTEIN FUNCTION; PROTEIN LOCALIZATION;

AMINO ACID MOTIFS; AMINO ACID SUBSTITUTION; ANIMALS; CELL NUCLEUS; CHO CELLS; CLEIDOCRANIAL DYSPLASIA; CORE BINDING FACTOR ALPHA 1 SUBUNIT; CORE BINDING FACTOR ALPHA 2 SUBUNIT; CORE BINDING FACTOR BETA SUBUNIT; CRICETINAE; CRICETULUS; DNA; HELA CELLS; HUMANS; MUTANT PROTEINS; MUTATION; PROTEIN BINDING; PROTEIN MULTIMERIZATION; PROTEIN STRUCTURE, TERTIARY; PROTEIN TRANSPORT; TRANSCRIPTIONAL ACTIVATION;

EID: 77951744137     PISSN: 07302312     EISSN: 10974644     Source Type: Journal    
DOI: 10.1002/jcb.22516     Document Type: Article

References (38)

1. Bae S-C, Ogawa E, Mauyama M, Oka H, Satake M, Shigesada K, Jenkins NA, Gilbert DJm, Copeland NG, Ito Y. 1994. PEBP2αB/mouse AML1 consists of multiple isoforms that possess differential transactivation potentials. Mol cell Biol 14:3242-3252. (Pubitemid 24132737)
2. Banerjee C, McCabe LR, Choi J-Y, Hiebert SW, Stein JL, Stein GS, Lian JB. 1997. Runt homology domain proteins in osteoblast differentiation: AML3/CBFA1 is a major component of a bone-specific complex. J Cell Biochem 66:1-8. (Pubitemid 27284091)
3. Choi J-Y, Pratap J, Javed A, Zaidi SK, Xing L, Balint E, Dalamangas S, Boyce B, van Wijnen AJ, Lian JB, Stein JL, Jones SN, Stein GS. 2001. Subnuclear targeting of Runx/Cbfa/AML factors is essential for tissue-specific differentiation during embryonic development. Proc Natl Acad Sci USA 98:8650-8655. (Pubitemid 32678082)
4. Crute BE, Lewis AF, Wu Z, Bushweller JH, Speck NA. 1996. Biochemical and biophysical proterties of the core-binding factor alpha2 (AML1) DNA-binding domain. J Biol Chem 271:26251-26260. (Pubitemid 26347474)
5. Cunningham ML, Seto ML, Hing AV, Bull MJ, Hopkin RJ, Leppig KA. 2006. Cleidocranial dysplasia with severe parietal bone dysplasia: C-terminal RUNX2 mutations. Birth Defects Research (Part A) 76:78-85.
6. Ducy P, Zhang R, Geoffroy V, Ridall AL, karsenty G. 1997. Osf2/Cbfa1: A transcriptional activator of osteoblast differentiation. Cell 89:747-754.
7. Galindo M, Pratap J, Young DW, Hovhannisyan H, Im H-J., Choi J-Y., Lian JB, Stein JL, Stein GS, van Wijnen AJ. 2005. The bone-specific expression of Runx2 oscillates during the cell cycle to support a G1-related antiproliferative function in osteoblasts. J Biol Chem 27:20274-20285. (Pubitemid 40776725)
8. Javed A, Guo B, Hiebert S, Choi J-Y, Green J, Zhao SC, Osborne MA, Stifani S, Stein JL, Lian JB, van Wijnen AJ, Stein GS. 2000. Groucho/TLE/R-esp proteins associate with the nuclear matrix and repress RUNX (CBF(alpha)/AML/ PEBP2(alpha)) dependent activation of tissue-specific gene transcription. J Cell Sci 113:2221-2231. (Pubitemid 30426836)
9. Kagoshima H, Shigesada K, Satake M, Ito Y, Miyoshi H, Ohki M, Pepling M, Gergen P. 1993. The Runt domain identifies a new family of heteromeric transcriptional regulators. Trend Genet 9:338-341. (Pubitemid 23296286)
10. Kim HJ, Kim JH, Bae SC, Choi J-Y, Kim HJ, Ryoo HM. 2003. The protein kinase C pathway plays a central role in the fibroblast growth factor-stimulated expression and transactivation activity of Runx2. J Biol Chem 278:319-326.
11. Kim HJ, Nam SH, Kim HJ, Park HS, Ryoo HM, Kim SY, Cho TJ, Kim SG, Bae SC, Kim IS, Stein JL, van Wijnen AJ, Stein GS, Lian JB, Choi J-Y. 2006. Four novel RUNX2 mutations including a splice donor site result in the cleidocranial dysplasia phenotype. J Cell Physiol 207:114-122.
12. Komori T, Yagi H, Nomura S, Yamaguchi A, Sasaki K, Deguchi K, Shimizu Y, Bronson RT, Gao YH, Inada M, Sato M, Okamato R, Kitamura Y, Yoshiki S, Kishimoto T. 1997. Targeted disruption of Cbfa1 results in a complete lack of bone formation owing to maturational arrest of osteoblasts. Cell 89:755-764. (Pubitemid 27516178)
13. Lee B, Thirunavukkarasu K, Zhou L, Pastore L, Baldini A, Hecht J, Geoffroy V, Ducy P, Karsenty G. 1997. Missense mutations abolishing DNA binding of the osteoblast-specific transcription factor OSF2/CBFA1 in cleidocranial dysplasia. Nat Genet 16:307-310. (Pubitemid 27280218)
14. Li Y, Pan W, Xu W, He N, Chen X, Liu H, Darryl Quarles L, Zhou H, Xiao Z. 2009. RUNX2 mutations in Chinese patients with cleidocranial dysplasia. Mutagenesis 24:425-431.
15. Lian JB, Stein GS, Javed A, van Wijnen AJ, Stein JL, Montecino M, Hassan MQ, Gaur T, Lengner CJ, Young DW. 2006. Networks and hubs for the transcriptional control of osteoblastogenesis. Rev Endocr Metab Disord 7:1-16. (Pubitemid 46044345)
16. Lou Y, Javed A, Hussain S, Colby J, Frederick D, Pratap J, Xie R, Gaur T, van Wijnen AJ, Jones SN, Stein GS, Lian JB, Stein JL. 2009. A Runx2 threshold for the cleidocranial dysplasia phenotype. Hum Mol Genet 18:556-568.
17. Matheny CJ, Speck ME, Cushing PR, Zhou Y, Corpora T, Regan M, Newman M, Roudaia L, Speck CL, Gu T-L, Griffey SM, Bushweller JH, Speck NA. 2007. Disease mutations in RUNX1 and RUNX2 create nonfunctional, dominant-negative, or hypomorphic alleles. EMBO J 26:1163-1175. (Pubitemid 46303591)
18. Mundlos S, Otto F, Mundlos C, Mulliken JB, Aylsworth AS, Albright S, Lindhout D, Cole WG, Henn W, Knoll JHM, Owen MJ, Mertelsmann R, Zabel BU, Olsen BR. 1997. Mutations involving the transcription factor CBFA1 cause cleidocranial dysplasia. Cell 89:773-779. (Pubitemid 27516180)
19. Nagata T, Werner MH. 2001. Functional mutagenesis of AML1/RUNX1 and PEBP2 beta/CBF beta define distinct, non-overlapping sites for DNA recognition and heterodimerization by the Runt domain. J Mol Biol 308:191-203. (Pubitemid 33043564)
20. Osato M, Asou N, Abdalla E, Hoshino K, Yamasaki H, Okubo T, Suzushima H, Takatsuki K, Kanno T, Shigesada K, Ito Y. 1999. Biallelic and heterozygous point mutations in the Runt domain of the AML1/PEBP2aB gene associated with myeloblastic leukemias. Blood 93:1817-1824. (Pubitemid 29128481)
21. Otto F, Thornell AP, Crompton T, Denzel A, Gilmour KC, Rosewell IR, Stamp GWH, Beddington RSP, Mundlos S, Olsen BR, Selby PB, Owen MJ. 1997. Cbfa1, a candidate gene for cleidocranial dysplasia syndrome, is essential for osteoblast differentiation and bone development. Cell 89:765-771. (Pubitemid 27516179)
22. Otto F, Kanegane H, Mundlos S. 2002. Mutations in the RUNX2 gene in patients with cleidocranial dysplasia. Hum Mutat 19:209-216. (Pubitemid 34195181)
23. Pratap J, Galindo M, Zaidi SK, Vradii D, Bhat BM, Robinson JA, Choi J-Y, Komori T, Stein JL, Lian JB, Stein GS, van Wijnen AJ. 2003. Cell growth regulatory role of Runx2 during proliferative expansion of pre-osteoblasts. Cancer Res 63:5357-5362. (Pubitemid 37139851)
24. Puppin C, Pellizzari L, Fabbro D, Fogolari F, Tell G, Tessa A, Santorelli FM, Damante G. 2005. Functional analysis of a novel RUNX2 missense mutation found in a family with cleidocranial dysplasia. J Hum Genet 50:679-683. (Pubitemid 41768792)
25. Quack I, Vonderstrass B, Stock M, Aylsworth AS, Becker A, Brueton L, Lee PJ, Majewski F, Mulliken JB, Suri M, Zenker M, Mundlos S, Otto F. 1999. Mutation analysis of core binding factor A1 in patients with cleidocranial dysplasia. Am J Hum Genet 65:1268-1278. (Pubitemid 30460377)
26. Ryoo HM, Kang HY, Lee SK, Lee KE, Kim JW. 2010. RUNX2 mutations in cleidocranial dysplasia patients. Oral Dis in press.
27. Sakai N, Hasegawa H, Yamazaki Y, Ui K, Tokunaga K, Hirose R, Uchinuma E, Susami T, Takato T. 2002. A case of a Japanese patient with cleidocranial dysplasia possessing a mutation of CBFA1 gene. Craniofac Surg 13:31-34. (Pubitemid 34873939)
28. Tahirov TH, Inoue-Bungo T, Morii H, Fujikawa A, Sasaki M, Kimura K, Shiina M, Sato K, Kumasaka T, Yamamoto M, Ishii S, Ogata K. 2001. Structural analyses of DNA recognition by the AML1/Runx-1 Runt domain and its allosteric control by CBF-β. Cell 104:755-767. (Pubitemid 32241025)
29. Thirunavukkarasu K, Magajaan M, McLarren KW, Stifani S, Karsenty G. 1998. Two domains unique to osteoblast-specific transcription factor Osf2/Cbfa1 contribute to its transactivation function and its inability to heterodimerize with Cbf-β. Mol Cell Biol 18:4197-4208. (Pubitemid 28287943)
30. van Wijnen AJ, Stein GS, Gergen JP, Groner Y, Hiebert SW, Ito Y, Liu P, Neil JC, Ohki M, Speck N. 2004. Nomenclature for Runt-related (RUNX) proteins. Oncogene 23:4209-4210.
31. Yagi R, Chen LF, Shigesada K, Murakami Y, Ito Y. 1999. A WW domain-containing yes-associated protein (YAP) is a novel transcriptional co-activator. EMBO J 18:2551-2562. (Pubitemid 29213286)
32. Yoshida T, Kanegane H, Osato M, Yanagida M, Miyawaki T, Ito Y, Shigesada K. 2002. Functional analysis of RUNX2 mutations in Japanese patients with cleidocranial dysplasia demonstrates novel genotype-phenotype correlations. Am J Hum Genet 71:724-738. (Pubitemid 135750507)
33. Yoshida T, Kanegane H, Osato M, Yanagida M, Miyawaki T, Ito Y, Shigesada K. 2003. Functional analysis of RUNX2 mutations in cleidocranial dysplasia: Novel insights into genotype-phenotype correlations. Blood Cells Mol Dis 30:184-193. (Pubitemid 36539362)
34. Young DW, Hassan MQ, Pratap J, Galindo M, Zaidi SK, Lee SH, Yang X, Xie R, Javed A, Underwood JM, Furcinitti P, Imbalzano AN, Penman S, Nickerson JA, Montecino MA, Lian JB, Stein JL, van Wijnen AJ, Stein GS. 2007. Mitotic occupancy and lineage-specific transcriptional control of rRNA genes by Runx2. Nature 445:442-446. (Pubitemid 46160913)
35. Zaidi SK, Javed A, Choi J-Y, van Wijnen AJ, Stein JL, Lian JB, Stein GS. 2001. A specific targeting signal directs Runx2/Cbfa1 to subnuclear domains and contributes to transactivation of the osteocalcin gene. J Cell Sci 114:3093-3102. (Pubitemid 32910464)
36. Zaidi SK, Young DW, Choi J-Y, Pratap J, Javed A, Montecino M, Stein JL, Lian JB, van Wijnen AJ, Stein GS. 2004. Tyrosine phosphorylation controls Runx2-mediated subnuclear targeting of YAP to repress transcription. J Biol Chem 279:43363-43366.
37. Zhang YW, Yasui N, Ito K, Huang G, Fujii M, Hanai J, Nogami H, Ochi T, Miyazono K, Ito Y. 2000. A RUNX2/PEBP2alpha A/CBFA1 mutation displaying impaired transactivation and Smad interaction in cleidocranial dysplasia. Proc Natl Acad Sci USA 97:10549-10554.
38. Zhou G, Chen Y, Zhou L, Thirunavukkarasu K, Hecht J, Chitayat D, Gelb BD, Pirinen S, Berry SA, Greenberg CR, Karsenty G, Lee B. 1999. CBFA1 mutation analysis and functional correlation with phenotypic variability in cleidocranial dysplasia. Hum Mol Genet 8:2311-2316. (Pubitemid 29525347)