Title | Dissecting the unique role of the retinoblastoma tumor suppressor during cellular senescence. |
Publication Type | Journal Article |
Year of Publication | 2010 |
Authors | Chicas A, Wang X, Zhang C, McCurrach M, Zhao Z, Mert O, Dickins RA, Narita M, Zhang M, Lowe SW |
Journal | Cancer Cell |
Volume | 17 |
Issue | 4 |
Pagination | 376-87 |
Date Published | 2010 Apr 13 |
ISSN | 1878-3686 |
Keywords | Cellular Senescence, DNA Replication, DNA, Neoplasm, Gene Transfer Techniques, Genes, Tumor Suppressor, Genetic Vectors, Homeostasis, Humans, Retinoblastoma, Retinoblastoma Protein |
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. |
DOI | 10.1016/j.ccr.2010.01.023 |
Alternate Journal | Cancer Cell |
PubMed ID | 20385362 |
PubMed Central ID | PMC2889489 |
Grant List | / HHMI / Howard Hughes Medical Institute / United States 5F32AG027631 / AG / NIA NIH HHS / United States P30 CA008748 / CA / NCI NIH HHS / United States R01 AG016379-11 / AG / NIA NIH HHS / United States AG16379 / AG / NIA NIH HHS / United States R01 AG016379 / AG / NIA NIH HHS / United States R56 AG016379 / AG / NIA NIH HHS / United States F32 AG027631 / AG / NIA NIH HHS / United States |
Related Faculty:
Zhen Zhao, Ph.D.