Structural Evolution and Dynamics of the p53 Proteins

• Published in: Cold Spring Harbor perspectives in medicine 2017-04, Vol.7 (4), p.a028308
• Main Authors: Chillemi, Giovanni, Kehrloesser, Sebastian, Bernassola, Francesca, Desideri, Alessandro, Dötsch, Volker, Levine, Arnold J, Melino, Gerry
• Format: Article
• Language: English
• Subjects: Binding Sites; Humans; Molecular Dynamics Simulation; Promoter Regions, Genetic; Trans-Activators - genetics; Transcription Factors - chemistry; Transcription Factors - genetics; Tumor Protein p73 - chemistry; Tumor Protein p73 - genetics; Tumor Suppressor Protein p53 - chemistry; Tumor Suppressor Protein p53 - genetics; Tumor Suppressor Proteins - chemistry; Tumor Suppressor Proteins - genetics
• ISSN: 2157-1422; 2472-5412
• DOI: 10.1101/cshperspect.a028308

The family of the p53 tumor suppressive transcription factors includes p73 and p63 in addition to p53 itself. Given the high degree of amino-acid-sequence homology and structural organization shared by the p53 family members, they display some common features (i.e., induction of cell death, cell-cycle arrest, senescence, and metabolic regulation in response to cellular stress) as well as several distinct properties. Here, we describe the structural evolution of the family members with recent advances on the molecular dynamic studies of p53 itself. A crucial role of the carboxy-terminal domain in regulating the properties of the DNA-binding domain (DBD) supports an induced-fit mechanism, in which the binding of p53 on individual promoters is preferentially regulated by the over .