Structural Evolution and Dynamics of the p53 Proteins.
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 theKOFFoverKON.
CINECA, SCAI-SuperComputing Applications and Innovation Department, Rome 00185, Italy.
Giovanni
G
Chillemi
Institute of Biophysical Chemistry, Goethe University, 60438 Frankfurt am Main, Germany.
Sebastian
S
Kehrloesser
Department of Experimental Medicine and Surgery, University of Rome "Tor Vergata," 00133 Rome, Italy.
Francesca
F
Bernassola
Biology Department, University of Rome "Tor Vergata," 00133 Rome, Italy.
Alessandro
A
Desideri
Institute of Biophysical Chemistry, Goethe University, 60438 Frankfurt am Main, Germany.
Volker
V
Dötsch
Institute for Advanced Study, Princeton, New Jersey 08540.|Rutgers Cancer Institute of New Jersey, New Brunswick, New Jersey 08903.
Arnold J
AJ
Levine
Medical Research Council, Toxicology Unit, Leicester University, Leicester LE1 9HN, United Kingdom.
Gerry
G
Melino
D001665:Binding Sites; D006801:Humans; D056004:Molecular Dynamics Simulation; D011401:Promoter Regions, Genetic; D015534:Trans-Activators / Q000235:genetics; D014157:Transcription Factors / Q000737:chemistry / Q000235:genetics; D000072160:Tumor Protein p73 / Q000737:chemistry / Q000235:genetics; D016159:Tumor Suppressor Protein p53 / Q000737:chemistry* / Q000235:genetics*; D025521:Tumor Suppressor Proteins / Q000737:chemistry / Q000235:genetics
C495901:TP53 protein, human; C115051:TP63 protein, human; C000606460:TP73 protein, human; D015534:Trans-Activators; D014157:Transcription Factors; D000072160:Tumor Protein p73; D016159:Tumor Suppressor Protein p53; D025521:Tumor Suppressor Proteins