Key Points
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The retinoblastoma gene (RB) was the first tumour suppressor to be cloned, but the mechanism behind its role in tumour suppression remains unclear.
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The retinoblastoma protein (RB) has been implicated in many cellular processes, such as regulation of the cell cycle, DNA-damage responses, DNA repair, DNA replication, protection against apoptosis, and differentiation, all of which could contribute to its function as a tumour suppressor.
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RB is closely related to two genes in mice and humans (p107 and 130, which are not commonly mutated in tumours), which have been found to have partially redundant as well as opposing functions in genetic experiments in mice. Future studies are required to identify the similarities and differences between these proteins, which might explain the seemingly unique role of RB as a tumour suppressor.
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As retinoblastomas do not arise as a consequence of Rb loss in mice, this model system is not ideal for studying this disease. However, this model system has provided information regarding the role of RB, p107 and p130 in development and tumorigenesis. Further experiments with conditional knockouts, as well as inter-crossing experiments, will provide a better insight into their roles in biological processes.
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Biochemical experiments have provided information regarding the nature of various protein interactions with RB. Considering that there are more than 100 reported RB-binding proteins, much detailed structure/function mapping is required to clarify the biological relevance of all these interactions.
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RB has also been associated with tumour growth, based on studies in which a constitutively active Rb allele gives rise to dysplasia in transgenic mice.
Abstract
Since its discovery, the retinoblastoma (RB) tumour-suppressor protein has been a focal point of cancer research. Accumulating evidence indicates a complex role for RB in cell proliferation, differentiation and survival. To further complicate matters, proteins that are related to RB have redundant as well as antagonistic functions. Recent studies of knockout mice and cells that lack one or more of these proteins have begun to clarify their various context-specific functions and the unique activity of this tumour suppressor.
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Acknowledgements
We thank J. Settleman, S. van den Heuvel, N. Dyson, F. Dick, E. Morris and D. Dimova for helpful comments and/or reading of this manuscript. We also thank G. Klein and all previous and present members of the Harlow and Dyson laboratories for helpful discussions over the years. Finally, we apologize to all our colleagues whose interesting work we could not cite, due to space restrains.
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Glossary
- ECTOPIC CELL CYCLE
-
Unscheduled or inappropriate entry into the cell cycle.
- ECTOPIC S-PHASE CELLS
-
Unscheduled or inappropriate entry into S phase.
- CHIMAERA
-
An organism with a genetic mixture of cells, such as wild type and mutant.
- TELENCEPHALON
-
Evolutionarily, the most recently evolved part of the brain. It is the forebrain, which is involved in cognition, learning and memory.
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Classon, M., Harlow, E. The retinoblastoma tumour suppressor in development and cancer. Nat Rev Cancer 2, 910–917 (2002). https://doi.org/10.1038/nrc950
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DOI: https://doi.org/10.1038/nrc950
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