Understanding pRb: toward the necessary development of targeted treatments for retinoblastoma
Uma M. Sachdeva, Joan M. O’Brien
Uma M. Sachdeva, Joan M. O’Brien
Published February 1, 2012
Citation Information: J Clin Invest. 2012;122(2):425-434. https://doi.org/10.1172/JCI57114.
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Science in Medicine

Understanding pRb: toward the necessary development of targeted treatments for retinoblastoma

Abstract

Retinoblastoma is a pediatric retinal tumor initiated by biallelic inactivation of the retinoblastoma gene (RB1). RB1 was the first identified tumor suppressor gene and has defined roles in the regulation of cell cycle progression, DNA replication, and terminal differentiation. However, despite the abundance of work demonstrating the molecular function and identifying binding partners of pRb, the challenge facing molecular biologists and clinical oncologists is how to integrate this vast body of molecular knowledge into the development of targeted therapies for treatment of retinoblastoma. We propose that a more thorough genetic understanding of retinoblastoma would inform targeted treatment decisions and could improve outcomes and quality of life in children affected by this disease.

Authors

Uma M. Sachdeva, Joan M. O’Brien

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Figure 2

Regulation of E2F-dependent gene expression by pRb.

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Regulation of E2F-dependent gene expression by pRb. pRb binds to DNA-bou...
pRb binds to DNA-bound E2F transcriptional regulators and suppresses their target gene expression through recruitment of HDACs, co-repressors, and chromatin remodeling enzymes. It also serves to inhibit the binding of co-activating transcription factors to E2F-bound promoters. Genes regulated by pRb-E2F include regulators of cell cycle progression at the G1/S transition, enzymes required for DNA synthesis, proto-oncogenes, apoptosis regulators, and modifiers of pRb/E2F pathway activity (47, 57, 124, 125).