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Journal of Physiology and Biochemistry

, Volume 60, Issue 4, pp 287–307 | Cite as

p53: Twenty five years understanding the mechanism of genome protection

  • M. Gomez-Lazaro
  • F. J. Fernandez-Gomez
  • J. Jordán
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Abstract

This year the p53 protein, also known as “guardian of the genome”, turns twenty five years old. During this period the p53 knowledge have changed from an initial pro-oncogene activity to the tumorsupressor p53 function. p53 is activated upon stress signals, such as gamma irradiation, UV, hypoxia, virus infection, and DNA damage, leading to protection of cells by inducing target genes. The molecules activated by p53 induce cell cycle arrest, DNA repair to conserve the genome and apoptosis. The regulation of p53 functions is tightly controlled through several mechanisms including p53 transcription and translation, protein stability, post-translational modifications, and subcellular localization. In fact, mutations in p53 are the most frequent molecular alterations detected in human tumours. Furthermore, in some degenerative processes, fragmentation and oxidative damage in DNA take place, and in these situations p53 is involved. So, p53 is considered a pharmacological target, p53 overexpression induces apoptosis in cancer and its expression blockage protects cells against lethal insults.

Key words

Apoptosis Necrosis mdm2 Cancer Tumor suppressor Mutation 

Keywords

Apoptosis Necrosis mdm2 Cáncer Supresor tumoral Mutación 

Resumen

En este año, la proteína p53, también conocida como “el guardián del genoma”, cumple veinticinco años. Durante este periodo, el conocimiento sobre las funciones desempeñadas por p53 ha ido cambiando desde una actividad pro-oncogénica hasta su función oncosupresora. Esta proteína se activa en respuesta a estímulos de estrés como radiaciones gamma y ultravioleta, hipoxia, infección vírica y daño en el ADN, protegiendo a la célula mediante acción sobre sus genes diana. Las moléculas activadas por p53 inducen parada en ciclo celular y reparación del ADN con el fin de conservar el genoma o de inducir apoptosis. La regulación de las funciones de p53 está controlada estrechamente a través de varios mecanismos que incluyen la transcripción, traducción, estabilidad de la proteína por modificaciones posttranscripcionales y su localización subcelular. Una de las alteraciones moleculares detectadas con más frecuencia en los tumores humanos son las mutaciones en p53. Mas aún, en algunos procesos degenerativos, donde tiene lugar la fragmentación y el daño oxidativo en el ADN, la p53 está implicada. Así, se considera a la p53 como una posible diana farmacológica, ya que su sobreexpresión induce apoptosis en células cancerosas y el bloqueo de su expresión protege a las células contra daños letales.

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Copyright information

© Universidad de Navarra 2004

Authors and Affiliations

  • M. Gomez-Lazaro
    • 1
  • F. J. Fernandez-Gomez
    • 1
  • J. Jordán
    • 1
  1. 1.Centro Regional de Investigaciones Biomédicas, Facultad de MedicinaUniversidad de Castilla-La ManchaAlbaceteSpain

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