Retinoblastoma binding protein-1 (RBP1) is a Runx2 coactivator and promotes osteoblastic differentiation
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- 作者：David G Monroe (1)
John R Hawse (1)
Malayannan Subramaniam (1)
Thomas C Spelsberg (1) - 刊名：BMC Musculoskeletal Disorders
- 出版年：2010
- 出版时间：December 2010
- 年：2010
- 卷：11
- 期：1
- 全文大小：760KB
- 参考文献：1. Ducy P, Zhang R, Geoffroy V, Ridall AL, Karsenty G: Osf2/Cbfa1: a transcriptional activator of osteoblast differentiation. / Cell 1997, 89:747-54. CrossRef
2. 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: Targeted disruption of Cbfa1 results in a complete lack of bone formation owing to maturational arrest of osteoblasts. / Cell 1997, 89:755-64. CrossRef
3. Otto F, Thornell AP, Crompton T, Denzel A, Gilmour KC, Rosewell IR, Stamp GWH, Beddington RSP, Mundlos S, Olsen BR, Selby PB, Owen MJ: Cbfa1, a candidate gene for cleidocranial dysplasia syndrome, is essential for osteoblast differentiation and bone development. / Cell 1997, 89:765-71. CrossRef
4. Nakashima K, Zhou X, Kunkel G, Zhang Z, Deng JM, Behringer RR, Crombrugghe BD: The novel zinc finger-containing transcription factor osterix is required for osteoblast differentiation and bone formation. / Cell 2002, 108:17-9. CrossRef
5. Lai A, Lee JM, Yang WM, DeCaprio JA, Kaelin WGJ, Seto E, Branton PE: RBP1 recruits both histone deacetylase-dependent and -independent repression activities to retinoblastoma family proteins. / Mol Cell Biol 1999,19(10):6632-641.
6. Lai A, Marcellus RC, Corbeil HB, Branton PE: RBP1 induces growth arrest by repression of E2F-dependent transcription. / Oncogene 1999,18(12):2091-100. CrossRef
7. Fattaey AR, Helin K, Dembski MS, Dyson N, Harlow E, Vuocolo GA, Hanobik MG, Haskell KM, Oliff A, Defeo-Jones D: Characterization of the retinoblastoma binding proteins RBP1 and RBP2. / Oncogene 1993,8(11):3149-156.
8. Lai A, Kennedy BK, Barbie DA, Bertos NR, Yang XJ, Theberge MC, Tsai SC, Seto E, Zhang Y, Kuzmichev A, Lane WS, Reinberg D, Harlow E, Branton PE: RBP1 recruits the mSIN3-histone deacetylase complex to the pocket of retinoblastoma tumor suppressor family proteins found in limited discrete regions of the nucleus at growth arrest. / Mol Cell Biol 2001,21(8):2918-932. CrossRef
9. Wu MY, Tsai TF, Beaudet AL: Deficiency of Rbbp1/Arid4a and Rbbp1l1/Arid4b alters epigenetic modifications and suppresses an imprinting defect in the PWS/AS domain. / Genes Dev 2006,20(20):2859-870. CrossRef
10. Wu MY, Eldin KW, Beaudet AL: Identification of chromatin remodeling genes Arid4a and Arid4b as leukemia suppressor genes. / J Natl Cancer Inst 2008, 100:1247-259. CrossRef
11. Monroe DG, Secreto FJ, Hawse JR, Subramaniam M, Khosla S, Spelsberg TC: Estrogen receptor isoform-specific regulation of the retinoblastoma binding protein 1 (RBBP1) gene: roles of AF1 and enhancer elements. / J Biol Chem 2006, 281:28596-8604. CrossRef
12. Monroe DG, Getz BJ, Johnsen SA, Riggs BL, Khosla S, Spelsberg TC: Estrogen receptor isoform-specific regulation of endogenous gene expression in human osteoblastic cell lines expressing either ERalpha or ERbeta. / J Cell Biochem 2003, 90:315-26. CrossRef
13. Monroe DG, Secreto FJ, Malayannan S, Getz BJ, Khosla S, Spelsberg TC: Estrogen receptor alpha and beta heterodimers exert unique effects on estrogen- and tamoxifen-dependent gene expression in human U2OS osteosarcoma cells. / Mol Endocrinol 2005, 19:1555-568. CrossRef
14. Ducy P, Karsanty G: Two distinct osteoblast-specific cis-acting elements control expression of a mouse osteocalcin gene. / Mol Cell Biol 1995, 15:1858-869.
15. Binda O, Roy JS, Branton PE: RBP1 family proteins exhibit SUMOylation-dependent transcriptional repression and induce cell growth inhibition reminiscent of senescence. / Mol Cell Biol 2006,26(5):1917-931. CrossRef
16. Komori T: Regulation of osteoblast differentiation by transcription factors. / J Cell Biochem 2006, 99:1233-239. CrossRef
17. Stock M, Otto F: Control of RUNX2 isoform expression: the role of promoters and enhancers. / J Cell Biochem 2005, 95:506-17. CrossRef
18. Patsialou A, Wilsker D, Moran E: DNA-binding properties of ARID family proteins. / Nucleic Acids Res 2005,33(1):66-0. CrossRef
19. Lian JB, Stein GS, Javed A, van Wijnen AJ, Stein JL, Montecino M, Hassan MQ, Gaur T, Lengner CJ, Young DW: Networks and hubs for the transcriptional control of osteoblastogenesis. / Rev Endocr Metab Disord 2006, 7:1-6. CrossRef
20. Banerjee C, McCabe LR, Choi JY, Hiebert SW, Stein JL, Stein GS, Lian JB: Runt homology domain proteins in osteoblast differentiation: AML3/CBFA1 is a major component of a bone-specific complex. / J Cell Biochem 1997, 66:1-. CrossRef
21. Ji C, Casinghino S, Chang DJ, Chen Y, Javed A, Ito Y, Hiebert SW, Lian JB, Stein GS, McCarthy TL, Centrella M: CBFa(AML/PEBP2)-related elements in the TGF-B Type I receptor promoter and expression with osteoblast differentiation. r and expression with osteoblast differentiation. / J Cell Biochem 1998, 69:353-63. CrossRef
22. Westendorf JJ, Hiebert SW: Mammalian runt-domain proteins and their roles in hematopoiesis, osteogenesis, and leukemia. / J Cell Biochem Suppl 1999, 32/33:51-8. CrossRef
23. Mundlos S, Otto F, Mundlos C, Mulliken JB, Ayslworth AS, Albright S, Lindhout D, Cole WG, Henn W, Knoll JHM, Owen MJ, Mertelsmann R, Zabel BU, Olsen BR: Mutations involving the transcription factor CBAF1 cause cleidocranial dysplasia. / Cell 1997, 89:773-79. CrossRef
24. The pre-publication history for this paper can be accessed here:http://www.biomedcentral.com/1471-2474/11/104/prepub - 作者单位：David G Monroe (1)
John R Hawse (1)
Malayannan Subramaniam (1)
Thomas C Spelsberg (1)
1. Department of Biochemistry and Molecular Biology, Mayo Clinic College of Medicine, Rochester, Minnesota, 55905, USA
文摘
Background Numerous transcription factors are involved in the establishment and maintenance of the osteoblastic phenotype, such as Runx2, osterix and Dlx5. The transcription factor retinoblastoma binding protein-1 (RBP1) was recently identified as an estrogen regulated gene in an osteosarcoma cell model. Since the function of RBP1 in osteoblastic differentiation and mineralization is unknown, we investigated the role of RBP1 in these processes. Methods To create a cell model with suppressed RBP1 expression, primary calvarial osteoblasts were infected with a shRNA lentiviral vector specific for mouse RBP1 (CalOB-ΔRBP1) or a scrambled control shRNA lentivirus (CalOB-Control). Stable cell lines were generated and their mineralization potential was determined using osteoblastic differentiation medium, Alizarin Red staining, and quantitative PCR (QPCR) analyses. Runx2 coactivation by RBP1 was determined through the use of transient transfection assays. Results Stable expression of the RBP1 shRNA lentivirus in CalOB-ΔRBP1 cells resulted in a 65-70% suppression of RBP1 expression. Osteoblastic mineralization assays demonstrated that suppression of RBP1 results in a potent delay in osteoblastic nodule formation in the CalOB-ΔRBP1 cells with a concomitant decrease in the expression of the osteogenic transcription factors Runx2 and osterix, along with decreases in BMP2, alkaline phosphatase, osteocalcin and bone sialoprotein. Regulation of Runx2 expression by RBP1 was shown to be mediated through the proximal P2 Runx2 promoter. Furthermore, RBP1 was demonstrated to be a potent coactivator of Runx2 transcriptional activity on two known Runx2 reporter constructs. These data suggest that the expression and activity of Runx2 is critically dependent on the presence of RBP1. Conclusions This study is the first to demonstrate that RBP1 is an important mediator of the osteoblastic phenotype and clearly defines RBP1 as a novel transcription factor involved in the well known Runx2-osterix transcriptional cascade. As such, the effects of RBP1 on these processes are mediated through both regulation of Runx2 expression and transcriptional activity.