p53 pp 142-159 | Cite as

p53’s Dilemma in Transcription: Analysis by Microarrays

  • Karuppiah Kannan
  • Gideon Rechavi
  • David Givol
Part of the Molecular Biology Intelligence Unit book series (MBIU, volume 1)

Abstract

Protection against cancer by p53 is due mainly to its activity as a transcription factor. The function of p53 in transactivation of target genes is analyzed here with emphasis on the dilemma between cell growth arrest and apoptosis pathways. The question as to which of these p53 functions is required for tumor suppression in vivo is revisited in light of new studies that renew the focus on senescence and growth arrest mechanisms in the protection against cancer. Global gene expression analysis by microarrays, employing either transcription or conformation switches for p53 activation were utilized to distinguish primary (direct) p53 targets from secondary (indirect) ones, and to probe pathways of inhibition of p53-induced apoptosis. The profile of gene expression indicates that p53 is a central node in the cellular network of growth control modulation and its activation results in altered expression of more than a thousand genes. Some of these are co-activators of p53 and may be involved in the decision making of the choice between p53 functions. The major conclusion is that the response to p53 activation is heterogeneous and is mainly dependent on the cellular context, which is evident from the pattern of p53-induced genes in different cell types and in various organs in response to irradiation. The analysis of gene expression profiles following activation or suppression of apoptosis by either chemotherapy or cytokines, respectively, may facilitate the identification of ways to bypass the loss of p53 activity and to design new modalities for cancer treatment.

Keywords

Adenoma Cysteine Doxorubicin Val135 Quinone 

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Copyright information

© Landes Bioscience and Springer Science+Business Media, LLC 2010

Authors and Affiliations

  • Karuppiah Kannan
    • 1
  • Gideon Rechavi
  • David Givol
  1. 1.Cancer PharmacologyMillennium Pharmaceuticals Inc.CambridgeUSA

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