Retinoblastoma protein positively regulates terminal adipocyte differentiation through direct interaction with C/EBPs

Phang Lang Chen, Daniel J. Riley, Yumay Chen, Wen Hwa Lee

Research output: Contribution to journalArticlepeer-review

377 Scopus citations

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/EBPβ-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.

Original languageEnglish (US)
Pages (from-to)2794-2804
Number of pages11
JournalGenes and Development
Volume10
Issue number21
DOIs
StatePublished - 1996

Keywords

  • C/EBP
  • adipocyte differentiation
  • cell cycle
  • transcription factors
  • tumor suppressor protein

ASJC Scopus subject areas

  • Genetics
  • Developmental Biology

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