Unknown,Transcriptomics,Genomics,Proteomics

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Genome-wide analysis of RB and p130 binding in human diploid fibroblasts


ABSTRACT: The action of RB as a tumor suppressor has been difficult to define, in part, due to the redundancy of the related proteins p107 and p130. By coupling advanced RNAi technology with a genome wide analysis of gene expression and RB chromatin binding, we identified a unique and specific activity of RB in repressing DNA replication as cells exit the cell cycle into senescence, a tumor suppressive program. Binding of RB was examined in growing, quiescent, senescent or senescent cells lackign RB. Binding of p130 was examined in quiescent or senescent cells in the presence or absence of RB. Libraries were prapered from DNA co-precipiated with RB or p130 specific antibodies or from mock (beads-only) immunoprecipiates.

ORGANISM(S): Homo sapiens

SUBMITTER: Agustin Chicas 

PROVIDER: E-GEOD-19898 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Publications

Dissecting the unique role of the retinoblastoma tumor suppressor during cellular senescence.

Chicas Agustin A   Wang Xiaowo X   Zhang Chaolin C   McCurrach Mila M   Zhao Zhen Z   Mert Ozlem O   Dickins Ross A RA   Narita Masashi M   Zhang Michael M   Lowe Scott W SW  

Cancer cell 20100401 4


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 fo  ...[more]

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