Distinct roles for p107 and p130 in Rb-independent cellular senescence.

Cell Cycle
Brian D LehmannDavid M Terrian

Abstract

Telomere attrition, DNA damage and constitutive mitogenic signaling can all trigger cellular senescence in normal cells and serve as a defense against tumor progression. Cancer cells may circumvent this cellular defense by acquiring genetic mutations in checkpoint proteins responsible for regulating permanent cell cycle arrest. A small family of tumor suppressor genes encoding the retinoblastoma susceptibility protein family (Rb, p107, p130) exerts a partially redundant control of entry into S phase of DNA replication and cellular proliferation. Here we report that activation of the p53-dependent DNA damage response has been found to accelerate senescence in human prostate cancer cells lacking a functional Rb protein. This novel form of irradiation-induced premature cellular senescence reinforces the notion that other Rb family members may compensate for loss of Rb protein in the DNA damage response pathway. Consistent with this hypothesis, depletion of p107 potently inhibits the irradiation-induced senescence observed in DU145 cells. In contrast, p130 depletion triggers a robust and unexpected form of premature senescence in unirradiated cells. The dominant effect of depleting both p107 and p130, in the absence of Rb, was a co...Continue Reading

Citations

Aug 12, 2009·Cell Research·Francesco P FiorentinoAntonio Giordano
Mar 9, 2010·Cell Division·Richa SinghYogeshwer Shukla
Dec 4, 2013·Cell Cycle·Tatiana V PospelovaValery A Pospelov
Apr 14, 2010·Cancer Cell·Christin E Burd, Norman E Sharpless
Oct 19, 2016·Molecular Biology Reports·Menderes Yusuf TerziBulent Gogebakan
May 3, 2014·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Anni Laine, Jukka Westermarck
May 15, 2021·Mutation Research. Genetic Toxicology and Environmental Mutagenesis·Fotini PapachristouAlexandra Tsaroucha

❮ Previous
Next ❯

Related Concepts

Related Feeds

Cell Checkpoints & Regulators

Cell cycle checkpoints are a series of complex checkpoint mechanisms that detect DNA abnormalities and ensure that DNA replication and repair are complete before cell division. They are primarily regulated by cyclins, cyclin-dependent kinases, and the anaphase-promoting complex/cyclosome. Here is the latest research.