2008 AFAR Research Grant: Protein Phosphatases in the Regulation of ATM-p53 Signaling Pathway and Cell Senescence

Please give a brief summary of your AFAR research project.
Cell senescence is triggered by internal and external stresses. ATM-p53 DNA damage response pathway has been shown to connect these stress signals with cellular senescence. Our previous studies showed that Wip1 phosphatase is a primary inhibitor for the ATM-p53 pathway. Removal of Wip1 induces cell senescence in primary mouse cells. In this project, we will first determine mechanisms by which Wip1 regulates the ATM-p53 pathway in senescent human cells. Second, we will identify novel protein phosphatases that are involved in the ATM-p53 signaling and cell senescence.

What problems are you addressing and what specific questions will your research seek to answer?
Many studies have been done on the activation of the ATM-p53 pathway, but little is known about how this pathway is shut off. We attempt to answer this question: whether and how protein phosphatases regulate cell senescence by inhibiting the ATM-p53 pathway.

What aspects of your project are most interesting from a scientific point of view?
The most interesting part of my research is to identify novel phosphatases that function as negative regulators in the process of cell senescence.

What are the implications of your research for age-related diseases and disorders?
Our research will help us and other researchers better understand molecular mechanisms in ageing and age-related disorders. Second, Wip1 knockout animals are potentially a good model to study organismal ageing.

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