title: Another fork in the road--life or death decisions by the tumour suppressor p53.
abstract: In response to cellular stress signals, the tumour suppressor p53 accumulates and triggers a host of antineoplastic responses. For instance, DNA damage activates two main p53-dependent responses: cell cycle arrest and attendant DNA repair or apoptosis (cell death). It is broadly accepted that, in response to DNA damage, the function of p53 as a sequence-specific transcription factor is crucial for tumour suppression. The molecular determinants, however, that favour the initiation of either a p53-dependent cell cycle arrest (life) or apoptotic (death) transcriptional programme remain elusive. Gaining a clear understanding of the mechanisms controlling cell fate determination by p53 could lead to the identification of molecular targets for therapy, which could selectively sensitize cancer cells to apoptosis. This review summarizes the literature addressing this important question in the field. Special emphasis is given to the role of the p53 response element, post-translational modifications and protein-protein interactions on cell fate decisions made by p53 in response to DNA damage.
authors.affiliation: Department of Oncological Sciences, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, Box 1130, New York, New York 10029, USA.
authors.forename: Luis A
authors.initials: LA
authors.lastname: Carvajal
authors.forename: James J
authors.initials: JJ
authors.lastname: Manfredi
mesh_terms: D000818:Animals; D017209:Apoptosis; D059447:Cell Cycle Checkpoints; D005786:Gene Expression Regulation; D006801:Humans; D009369:Neoplasms / Q000378:metabolism; D011401:Promoter Regions, Genetic; D011499:Protein Processing, Post-Translational; D013312:Stress, Physiological; D014158:Transcription, Genetic; D016159:Tumor Suppressor Protein p53 / Q000502:physiology*
chemical_list: C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53