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The Retinoblastoma Gene Family in Cell Cycle Regulation and Suppression of Tumorigenesis

  • Jan-Hermen DannenbergEmail author
  • Hein P. J. te RieleEmail author
Chapter
Part of the Results and Problems in Cell Differentiation book series (RESULTS, volume 42)

Abstract

Since its discovery in 1986, as the first tumor suppressor gene, the retinoblastoma gene (Rb) has been extensively studied. Numerous biochemical and genetic studies have elucidated in great detail the function of the Rb gene and placed it at the heart of the molecular machinery controlling the cell cycle. As more insight was gained into the genetic events required for oncogenic transformation, it became clear that the retinoblastoma gene is connected to biochemical pathways that are dysfunctional in virtually all tumor types. Besides regulating the E2F transcription factors, pRb is involved in numerous biological processes such as apoptosis, DNA repair, chromatin modification, and differentiation. Further complexity was added to the system with the discovery of p107 and p130, two close homologs of Rb. Although the three family members share similar functions, it is becoming clear that these proteins also have unique functions in differentiation and regulation of transcription. In contrast to Rb, p107 and p130 are rarely found inactivated in human tumors. Yet, evidence is accumulating that these proteins are part of a “tumor-surveillance” mechanism and can suppress tumorigenesis. Here we provide an overview of the knowledge obtained from studies involving the retinoblastoma gene family with particular focus on its role in suppressing tumorigenesis.

Keywords

Retinoblastoma Protein bHLH Transcription Factor Pocket Protein preB Cell Increase Cell Turnover 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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Notes

Acknowledgments

We thank our colleagues Floris Foijer, Jacob Hansen, René Medema, Daniel Peeper, Rob Wolthuis and many others for helpful discussions related to this chapter. Work in the Te Riele lab is supported by grants from the Dutch Cancer Society, the European Commission and the Netherlands Genomics Initiative.

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Authors and Affiliations

  1. 1.Department of Medical OncologyDana-Farber Cancer Institute and Harvard Medical SchoolBoston, MassachusettsUSA
  2. 2.Department of Molecular BiologyNetherlands Cancer InstituteAmsterdamThe Netherlands

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