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Research Papers
Institute of Biotechnology, The University of Texas Health Science Center at San Antonio 78245, USA.
Abstract
To define a mechanism by which retinoblastoma protein (Rb) functions in cellular differentiation, we studied primary fibroblasts from the lung buds of wild-type (RB+/+) and null-mutant (RB-/-) mouse embryos. In culture, the RB+/+ fibroblasts differentiated into fat-storing cells, either spontaneously or in response to hormonal induction; otherwise syngenic RB-/- fibroblasts cultured in identical conditions did not. Ectopic expression of normal Rb, but not Rb with a single point mutation, enabled RB-/- fibroblasts to differentiate into adipocytes. Rb appears in murine fibroblasts to activate CCAAT/enhancer-binding proteins (C/EBPs), a family of transcription factors crucial for adipocyte differentiation. Physical interaction between Rb and C/EBPs was demonstrated by reciprocal coimmunoprecipitation, but occurred only in differentiating cells. Wild-type Rb also enhanced the binding of C/EBP to cognate DNA sequences in vitro and the transactivation of a C/EBPbeta-responsive promoter in cells. Taken together, these observations establish a direct and positive role for Rb in terminal differentiation. Such a role contrasts with the function of Rb in arresting cell cycle progression in G1 by negative regulation of other transcription factors like E2F-1.
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V. D. Brown and B. L. Gallie The B-Domain Lysine Patch of pRB Is Required for Binding to Large T Antigen and Release of E2F by Phosphorylation Mol. Cell. Biol., March 1, 2002; 22(5): 1390 - 1401. [Abstract] [Full Text] [PDF] |
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R. M. Melillo, G. M. Pierantoni, S. Scala, S. Battista, M. Fedele, A. Stella, M. C. De Biasio, G. Chiappetta, V. Fidanza, G. Condorelli, et al. Critical Role of the HMGI(Y) Proteins in Adipocytic Cell Growth and Differentiation Mol. Cell. Biol., April 1, 2001; 21(7): 2485 - 2495. [Abstract] [Full Text] |
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A. Yu. Nikitin, B. Shan, A. Flesken-Nikitin, K.-H. Chang, and W.-H. Lee The Retinoblastoma Gene Regulates Somatic Growth during Mouse Development Cancer Res., April 1, 2001; 61(7): 3110 - 3118. [Abstract] [Full Text] |
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H. Müller, A. P. Bracken, R. Vernell, M. C. Moroni, F. Christians, E. Grassilli, E. Prosperini, E. Vigo, J. D. Oliner, and K. Helin E2Fs regulate the expression of genes involved in differentiation, development, proliferation, and apoptosis Genes & Dev., February 1, 2001; 15(3): 267 - 285. [Abstract] [Full Text] |
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S. Shimba, T. Wada, and M. Tezuka Arylhydrocarbon receptor (AhR) is involved in negative regulation of adipose differentiation in 3T3-L1 cells: AhR inhibits adipose differentiation independently of dioxin J. Cell Sci., January 8, 2001; 114(15): 2809 - 2817. [Abstract] [Full Text] [PDF] |
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H. A. Hirsch, L. Gu, and R. W. Henry The Retinoblastoma Tumor Suppressor Protein Targets Distinct General Transcription Factors To Regulate RNA Polymerase III Gene Expression Mol. Cell. Biol., December 15, 2000; 20(24): 9182 - 9191. [Abstract] [Full Text] |
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W. R. MacLellan, G. Xiao, M. Abdellatif, and M. D. Schneider A Novel Rb- and p300-Binding Protein Inhibits Transactivation by MyoD Mol. Cell. Biol., December 1, 2000; 20(23): 8903 - 8915. [Abstract] [Full Text] |
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M. Classon, B. K. Kennedy, R. Mulloy, and E. Harlow Opposing roles of pRB and p107 in adipocyte differentiation PNAS, September 19, 2000; (2000) 190343597. [Abstract] [Full Text] |
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C. Lemercier, K. Duncliffe, I. Boibessot, H. Zhang, A. Verdel, D. Angelov, and S. Khochbin Involvement of Retinoblastoma Protein and HBP1 in Histone H10 Gene Expression Mol. Cell. Biol., September 15, 2000; 20(18): 6627 - 6637. [Abstract] [Full Text] |
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