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Publication : Perp is a mediator of p53-dependent apoptosis in diverse cell types.

First Author  Ihrie RA Year  2003
Journal  Curr Biol Volume  13
Issue  22 Pages  1985-90
PubMed ID  14614825 Mgi Jnum  J:86549
Mgi Id  MGI:2680748 Doi  10.1016/j.cub.2003.10.055
Citation  Ihrie RA, et al. (2003) Perp is a mediator of p53-dependent apoptosis in diverse cell types. Curr Biol 13(22):1985-90
abstractText  The induction of apoptosis by the p53 protein is critical for its activity as a tumor suppressor. Although it is clear that p53 induces apoptosis at least in part by direct transcriptional activation of target genes, the set of p53 target genes that mediate p53 function in apoptosis in vivo remains to be well defined. The Perp (p53 apoptosis effector related to PMP-22) gene is highly expressed in cells undergoing p53-dependent apoptosis as compared to cells undergoing p53-dependent G1 arrest. Perp is a direct p53 target, and its overexpression is sufficient to induce cell death in fibroblasts, implicating it as an important component of p53 apoptotic function. Here, through the generation of Perp-deficient mice, we analyze the role of Perp in the p53 apoptosis pathway in multiple primary cell types by comparing the cell death responses of Perp null cells to those of wild-type and p53 null cells. These experiments demonstrate the involvement of Perp in p53-mediated cell death in thymocytes and neurons but not in E1A-expressing MEFs, indicating a cell type-specific role for Perp in the p53 cell death pathway. In addition, we show that Perp is not required for proliferation-associated functions of p53. Thus, Perp selectively mediates the p53 apoptotic response, and the requirement for Perp is dictated by cellular context.
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