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 5

Regulation of pRb in coordination with the cell cycle.

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Regulation of pRb in coordination with the cell cycle. Quiescent cells c...
Quiescent cells contain hypophosphorylated, active pRb. (A) In response to mitogenic signaling, cylin D–CDK4 complexes phosphorylate pRb and promote its subsequent phosphorylation by cyclin E–CDK2 in late G1 (28, 126, 127). These phosphorylation events result in inactivation of pRb, allowing progression of the cell cycle past the G1/S transition and promoting DNA replication during S phase. pRb is further phosphorylated during G2/M phases of the cell cycle (56, 59, 60). As mitosis comes to completion, pRb is de-phosphorylated and returns to its active, hypophosphorylated state. (B) In response to antiproliferative signals (red), CDKi, including Ink4 and Cip/Kip family members, are activated, resulting in inhibition of cyclin-CDK complexes and promoting pRb activity to cause G1 arrest and cell cycle exit.