Encyclopedia of Cancer

Living Edition
| Editors: Manfred Schwab

Gain-of-Function p53

  • Giovanni BlandinoEmail author
Living reference work entry
DOI: https://doi.org/10.1007/978-3-642-27841-9_2302-2


Gain of function is the property of some proteins whose alterations determine the acquisition of novel functions mainly opposite to those exerted by the wild-type counterparts.


The gene product of the tumor suppressor p53 represents a paradigm of a protein whose alterations, mainly missense mutations, cause the acquisition of novel functions that contribute to the insurgence, the maintenance, the spreading, and the chemoresistance of certain tumors. p53 is a transcription factorthat can be roughly divided in three functional domains: (i) the N-terminus where the transcriptional activity resides, (ii) the central DNA-binding domain that is responsible for the specific recognition of p53 binding sites, and (iii) the C-terminus domain that exerts oligomeric and autoregulatory activities. Half of human cancers bear p53 mutations that mainly occur within the specific DNA-binding domain. The resulting proteins are characterized by the loss of the antitumoral...

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  1. Di Agostino S, Strano S, Emiliozzi V et al (2006) Gain of function of mutant p53: the mutant p53/NFY protein complex reveals an aberrant transcriptional mechanism of cell cycle regulation. Cancer Cell 3:191–202CrossRefGoogle Scholar
  2. Sigal A, Rotter V (2000) Oncogenic mutations of the p53 tumor suppressor: the demons of the guardian of the genome. Cancer Res 60:6788–6793PubMedGoogle Scholar
  3. Soussi T, Beroud C (2001) Assessing TP53 status in human tumours to evaluate clinical outcome. Nat Rev Cancer 1:233–240CrossRefPubMedGoogle Scholar
  4. Strano S, Dell’Orso S, Di Agostino S et al (2007) Mutant p53: an oncogenic transcription factor. Oncogene 26:2212–2219CrossRefPubMedGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2015

Authors and Affiliations

  1. 1.Translational Oncogenomic LaboratoryRegina Elena Cancer InstituteRomeItaly