P53, Cell Cycle Arrest and Apoptosis


The p53 gene, first described in 1979, was the first tumor suppressor gene to be identified (Lane and Crawford, 1979; Linzer and Levine, 1979). It was originally identified as an oncogene- a cell cycle accelerator, but subsequent studies ten years after its discovery confirmed it to be a tumor suppressor gene that is highly mutated in a wide variety of tumors (Baker et al., 1990; Finlay et al., 1989). In about half of the tumors, p53 is inactivated directly as a result of mutations in the p53 gene. In many others, it is inactivated indirectly through binding to viral proteins, or as a result of alterations in the genes whose products interact with p53 or transmit information to or from p53. The tumor suppressor protein p53 acts as a major node in a complex signaling pathway that evolved to sense a broad range of cellular stresses such as DNA damage, oncogene activation, nucleotide depletion, and hypoxia (Figure 1). In the absence of cellular stress, the p53 protein is expressed at low steady-state levels and exerts little, if any, effect on cell fate.


Cell Cycle Arrest Death Receptor Cell Death Differ Trail Sensitivity Autoregulatory Feedback Loop 
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© Springer 2007

Authors and Affiliations

  1. 1.Departments of Medicine, Genetics, Pharmacology, and Abramson Cancer CenterUniversity of Pennsylvania School of MedicinePhiladelphiaUSA

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