Dissecting the Unique Role of the Retinoblastoma Tumor Suppressor during Cellular Senescence

Chicas, A., Wang, X., Zhang, C., McCurrach, M. E., Zhao, Z., Mert, O., Dickins, R. A., Narita, M., Zhang, M. Q., Lowe, S. W. (April 2010) Dissecting the Unique Role of the Retinoblastoma Tumor Suppressor during Cellular Senescence. Cancer Cell, 17 (4). pp. 376-387.

URL: http://www.ncbi.nlm.nih.gov/pubmed/20385362
DOI: 10.1016/j.ccr.2010.01.023

Abstract

The RB protein family (RB, p107, and p130) has overlapping and compensatory functions in cell-cycle control. However, cancer-associated mutations are almost exclusively found in RB, implying that RB has a nonredundant role in tumor suppression. We demonstrate that RB preferentially associates with E2F target genes involved in DNA replication and is uniquely required to repress these genes during senescence but not other growth states. Consequently, RB loss leads to inappropriate DNA synthesis following a senescence trigger and, together with disruption of a p21-mediated cell-cycle checkpoint, enables extensive proliferation and rampant genomic instability. Our results identify a nonredundant RB effector function that may contribute to tumor suppression and reveal how loss of RB and p53 cooperate to bypass senescence. © 2010 Elsevier Inc. All rights reserved.

Item Type: Paper
Uncontrolled Keywords: CELL CYCLE
Subjects: diseases & disorders > cancer
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > mutations
CSHL Authors:
Communities: CSHL labs > Lowe lab
CSHL labs > Zhang lab
CSHL Cancer Center Shared Resources > Bioinformatics Service
Watson School > Publications
CSHL Cancer Center Shared Resources > DNA Sequencing Service
CSHL Cancer Center Shared Resources > Flow Cytometry Service
CSHL Cancer Center Shared Resources > Instrumentation Service
CSHL Cancer Center Shared Resources > Microarray Service
CSHL Cancer Center Shared Resources > Microscopy Service
Depositing User: CSHL Librarian
Date: 12 April 2010
Date Deposited: 28 Sep 2011 14:55
Last Modified: 30 Dec 2014 16:11
PMCID: PMC2889489
Related URLs:
URI: http://repository.cshl.edu/id/eprint/15386

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