Abstracts
Résumé
L’homologie de structure et d’organisation génique existant entre p53 et ses deux homologues, p73 et p63, suggère des fonctions biologiques similaires. Néanmoins des différences notables existent entre les membres de la famille p53. Ainsi, p53 est fréquemment muté dans les cancers humains, contrairement à p73 et p63. De plus, à l’opposé de p53 dont le transcrit majoritaire couvre tous les exons du gène, p73 et p63 codent pour deux types d’isoformes aux effets biologiques opposés: les unes, contenant un domaine de transactivation (TAD), ont des propriétés de protéine suppresseur de tumeur, tandis que les autres, dépourvues de TAD, possèdent des propriétés oncogéniques. Par ailleurs, si p53 répond aux stimulus génotoxiques, ses homologues participent au développement et à la différenciation tissulaires: tissu neuronal pour p73, tissu épithélial pour p63. Mais les trois membres de la famille p53 peuvent coopérer étroitement lors de la réponse cellulaire consécutive à un dommage génotoxique. Les tumeurs neuroblastiques, qui reproduisent les différents stades de différenciation des cellules du système nerveux sympathique, constituent un modèle de choix pour étudier les relations entre p53 et p73, ainsi que la régulation de leur expression.
Summary
Homologies in sequence and gene organization of p53 and their relatives, p73 and p63, suggest similar biological functions. However differences exist between the p53 family members. Indeed in human tumors p53 is often mutated while p63 and p73 are very rarely mutated. In addition, in contrast to p53 which is transcribed in a unique mRNA species spanning all gene exons, each homologue expresses two types of isoforms: some with transactivation domain (TAD) showing tumor suppressive properties, the others deprived of TAD, with oncogenic properties. If p53 responds to immediate genotoxic stress, its homologues participate to the cell homeostasis of specific tissues along their development and differentiation, neuronal tissue for p73, epithelial for p63. However a collaboration between the three p53 family members has been shown to occur in response to cell genotoxic damages. Neuroblastic tumors characterized by a large spectrum of neuronal differentiation constitute a good model to study relationship between p73 and p53 as well as the regulation of their respective expression.
Appendices
Références
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