p53 isoforms - a conspiracy to kidnap p53 tumor suppressor activity?
For 25 years, the p53 tumor suppressor protein was considered the only protein expressed by the (TP53) gene. However, in several studies the existence of p53 alternative transcripts in mouse and human cells has been documented, while their expression patterns and functions remained a mystery. Since 2002, several groups have identified and described the existence of up to 10 p53 isoforms and have demonstrated their roles in modulation of p53 suppressive activity. It is now clear that the patterns of p53 expression are much more complex than previously recognized and that these isoforms have the potential to act either synergistically or antagonistically, depending on their structure and mechanism of production. This review focuses on the different ways to produce p53 isoforms, on their specific properties, on their effect on p53 suppressive activity as well as on their implication in a new potential mechanism involved in p53 deregulation in cancer.
International Agency for Research on Cancer, 150 cours Albert Thomas, 69372 Lyon Cedex 08, France.
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Marcel
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Hainaut
D017398:Alternative Splicing; D000818:Animals; D005786:Gene Expression Regulation; D006801:Humans; D008958:Models, Molecular; D009369:Neoplasms / Q000235:genetics / Q000378:metabolism; D020033:Protein Isoforms / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D017434:Protein Structure, Tertiary; D051736:Proto-Oncogene Proteins c-mdm2 / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology; D014158:Transcription, Genetic; D016159:Tumor Suppressor Protein p53 / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*
D020033:Protein Isoforms; D016159:Tumor Suppressor Protein p53; C497206:MDM2 protein, human; D051736:Proto-Oncogene Proteins c-mdm2