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Coordinated regulation of life and death by RB

Nature Reviews Cancer volume 3, pages 130–138 (2003)Cite this article

Key Points

  • Loss of RB sensitizes cells to apoptosis.

  • Ectopic apoptosis of Rb-null neurons is not a default outcome of inappropriate S-phase entry.

  • RB can be inactivated by phosphorylation and degradation.

  • RB degradation is required for tumour necrosis factor type I receptor-induced apoptosis.

  • Most sporadic human cancers inactivate RB function by exploiting pathways that regulate RB phosphorylation.

  • Loss of RB can only contribute to tumour development under conditions in which apoptosis response is compromised.

Abstract

Recent studies have shown that RB can inhibit apoptosis, independently of its ability to block cell proliferation. This poses the question of how cells choose to grow or to die when RB becomes inactivated. RB is phosphorylated following mitogenic stimulation, but it is degraded in response to death stimuli. Most sporadic cancers also inactivate RB by phosphorylation, rather than losing RB entirely — possibly to exploit the survival advantage conferred by RB under stress. Drawing from the different mechanisms of RB inactivation, we propose two models for ways in which cells use RB to make the choice of life versus death.

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Figure 1: Mechanisms of RB inactivation.
Figure 2: Genetic inactivation of Rb sensitizes developing neurons and skeletal muscle to apoptosis.
Figure 3: Two explanations for the apoptosis phenotype of Rb-null cells.
Figure 4: Two models for the differential regulation of proliferation versus apoptosis.

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Acknowledgements

We are grateful to the Wang lab members for stimulating discussion and critical reading of the manuscript throughout its preparation. B.N.C is supported by a postdoctoral fellowship from the Damon Runyon Cancer Research Foundation. This work is supported by a National Cancer Institute grant awarded to J.Y.J.W.

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Authors and Affiliations

  1. the Division of Biological Sciences and the Cancer Center, University of California, San Diego, La Jolla, 92093-0322, California, USA

    B. Nelson Chau & Jean Y.J. Wang

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  1. B. Nelson Chau
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  2. Jean Y.J. Wang
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Corresponding author

Correspondence to Jean Y.J. Wang.

Related links

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DATABASES

LocusLink

ABL

AKT

Apaf1

Casp3

CDK4

CDK6

Cdkn1a

CDKN2A

cyclin D1

E2f1

E2F1

E2f3

Id2

IKKβ

NF-κB

Rb

RB

RIP

TNF-α

TNFRI

TNFRII

Trp53

OMIM

hereditary retinoblastoma

FURTHER INFORMATION

CancerGeneticsWeb

Mouse Knockout and Mutation database

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Chau, B., Wang, J. Coordinated regulation of life and death by RB. Nat Rev Cancer 3, 130–138 (2003). https://doi.org/10.1038/nrc993

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