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...