title: The adapter protein CD2AP binds to p53 protein in the cytoplasm and can discriminate its polymorphic variants P72R.
abstract: Proline-rich motifs are widely distributed in eukaryotic proteomes and are usually involved in the assembly of functional complexes through interaction with specific binding modules. The tumour-suppressor p53 protein presents a proline-rich region that is crucial for regulating apoptosis by connecting the p53 with a complex protein network. In humans, a common polymorphism determines the identity of residue 72, either proline or arginine, and affects the features of the motifs present in the polyproline domain. The two isoforms have different biochemical properties and markedly influence cancer onset and progression. In this article, we analyse the binding of the p53 proline-rich region with a pool of selected polyproline binding domains (i.e. SH3 and WW), and we present the first demonstration that the purified SH3 domains of the CD2AP/Cin85 protein family are able to directly bind the p53 protein, and to discriminate between the two polymorphic variants P72R.
authors.affiliation: Department DiBEST, University of Calabria, Rende, 87036, Italy; DIMES, Department of Experimental, Diagnostic and Specialty Medicine, University of Bologna, Bologna 40126, Italy; CIG, Interdepartmental Center "Luigi Galvani", University of Bologna, Bologna 40126, Italy; Department of Biology, University of Rome Tor Vergata, Rome 00100, Italy; and Istituto Ricovero e Cura a Carattere Scientifico, Fondazione Santa Lucia, Rome, 00100, Italy simona.panni@unical.it.
authors.forename: Simona
authors.initials: S
authors.lastname: Panni
authors.affiliation: Department DiBEST, University of Calabria, Rende, 87036, Italy; DIMES, Department of Experimental, Diagnostic and Specialty Medicine, University of Bologna, Bologna 40126, Italy; CIG, Interdepartmental Center "Luigi Galvani", University of Bologna, Bologna 40126, Italy; Department of Biology, University of Rome Tor Vergata, Rome 00100, Italy; and Istituto Ricovero e Cura a Carattere Scientifico, Fondazione Santa Lucia, Rome, 00100, Italy Department DiBEST, University of Calabria, Rende, 87036, Italy; DIMES, Department of Experimental, Diagnostic and Specialty Medicine, University of Bologna, Bologna 40126, Italy; CIG, Interdepartmental Center "Luigi Galvani", University of Bologna, Bologna 40126, Italy; Department of Biology, University of Rome Tor Vergata, Rome 00100, Italy; and Istituto Ricovero e Cura a Carattere Scientifico, Fondazione Santa Lucia, Rome, 00100, Italy.
authors.forename: Stefano
authors.initials: S
authors.lastname: Salvioli
authors.affiliation: Department DiBEST, University of Calabria, Rende, 87036, Italy; DIMES, Department of Experimental, Diagnostic and Specialty Medicine, University of Bologna, Bologna 40126, Italy; CIG, Interdepartmental Center "Luigi Galvani", University of Bologna, Bologna 40126, Italy; Department of Biology, University of Rome Tor Vergata, Rome 00100, Italy; and Istituto Ricovero e Cura a Carattere Scientifico, Fondazione Santa Lucia, Rome, 00100, Italy.
authors.forename: Elena
authors.initials: E
authors.lastname: Santonico
authors.affiliation: Department DiBEST, University of Calabria, Rende, 87036, Italy; DIMES, Department of Experimental, Diagnostic and Specialty Medicine, University of Bologna, Bologna 40126, Italy; CIG, Interdepartmental Center "Luigi Galvani", University of Bologna, Bologna 40126, Italy; Department of Biology, University of Rome Tor Vergata, Rome 00100, Italy; and Istituto Ricovero e Cura a Carattere Scientifico, Fondazione Santa Lucia, Rome, 00100, Italy.
authors.forename: Francesca
authors.initials: F
authors.lastname: Langone
authors.affiliation: Department DiBEST, University of Calabria, Rende, 87036, Italy; DIMES, Department of Experimental, Diagnostic and Specialty Medicine, University of Bologna, Bologna 40126, Italy; CIG, Interdepartmental Center "Luigi Galvani", University of Bologna, Bologna 40126, Italy; Department of Biology, University of Rome Tor Vergata, Rome 00100, Italy; and Istituto Ricovero e Cura a Carattere Scientifico, Fondazione Santa Lucia, Rome, 00100, Italy.
authors.forename: Francesca
authors.initials: F
authors.lastname: Storino
authors.affiliation: Department DiBEST, University of Calabria, Rende, 87036, Italy; DIMES, Department of Experimental, Diagnostic and Specialty Medicine, University of Bologna, Bologna 40126, Italy; CIG, Interdepartmental Center "Luigi Galvani", University of Bologna, Bologna 40126, Italy; Department of Biology, University of Rome Tor Vergata, Rome 00100, Italy; and Istituto Ricovero e Cura a Carattere Scientifico, Fondazione Santa Lucia, Rome, 00100, Italy Department DiBEST, University of Calabria, Rende, 87036, Italy; DIMES, Department of Experimental, Diagnostic and Specialty Medicine, University of Bologna, Bologna 40126, Italy; CIG, Interdepartmental Center "Luigi Galvani", University of Bologna, Bologna 40126, Italy; Department of Biology, University of Rome Tor Vergata, Rome 00100, Italy; and Istituto Ricovero e Cura a Carattere Scientifico, Fondazione Santa Lucia, Rome, 00100, Italy.
authors.forename: Serena
authors.initials: S
authors.lastname: Altilia
authors.affiliation: Department DiBEST, University of Calabria, Rende, 87036, Italy; DIMES, Department of Experimental, Diagnostic and Specialty Medicine, University of Bologna, Bologna 40126, Italy; CIG, Interdepartmental Center "Luigi Galvani", University of Bologna, Bologna 40126, Italy; Department of Biology, University of Rome Tor Vergata, Rome 00100, Italy; and Istituto Ricovero e Cura a Carattere Scientifico, Fondazione Santa Lucia, Rome, 00100, Italy Department DiBEST, University of Calabria, Rende, 87036, Italy; DIMES, Department of Experimental, Diagnostic and Specialty Medicine, University of Bologna, Bologna 40126, Italy; CIG, Interdepartmental Center "Luigi Galvani", University of Bologna, Bologna 40126, Italy; Department of Biology, University of Rome Tor Vergata, Rome 00100, Italy; and Istituto Ricovero e Cura a Carattere Scientifico, Fondazione Santa Lucia, Rome, 00100, Italy.
authors.forename: Claudio
authors.initials: C
authors.lastname: Franceschi
authors.affiliation: Department DiBEST, University of Calabria, Rende, 87036, Italy; DIMES, Department of Experimental, Diagnostic and Specialty Medicine, University of Bologna, Bologna 40126, Italy; CIG, Interdepartmental Center "Luigi Galvani", University of Bologna, Bologna 40126, Italy; Department of Biology, University of Rome Tor Vergata, Rome 00100, Italy; and Istituto Ricovero e Cura a Carattere Scientifico, Fondazione Santa Lucia, Rome, 00100, Italy Department DiBEST, University of Calabria, Rende, 87036, Italy; DIMES, Department of Experimental, Diagnostic and Specialty Medicine, University of Bologna, Bologna 40126, Italy; CIG, Interdepartmental Center "Luigi Galvani", University of Bologna, Bologna 40126, Italy; Department of Biology, University of Rome Tor Vergata, Rome 00100, Italy; and Istituto Ricovero e Cura a Carattere Scientifico, Fondazione Santa Lucia, Rome, 00100, Italy.
authors.forename: Gianni
authors.initials: G
authors.lastname: Cesareni
authors.affiliation: Department DiBEST, University of Calabria, Rende, 87036, Italy; DIMES, Department of Experimental, Diagnostic and Specialty Medicine, University of Bologna, Bologna 40126, Italy; CIG, Interdepartmental Center "Luigi Galvani", University of Bologna, Bologna 40126, Italy; Department of Biology, University of Rome Tor Vergata, Rome 00100, Italy; and Istituto Ricovero e Cura a Carattere Scientifico, Fondazione Santa Lucia, Rome, 00100, Italy castagnoli@uniroma2.it.
authors.forename: Luisa
authors.initials: L
authors.lastname: Castagnoli
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics* / Q000378:metabolism; D020816:Amino Acid Motifs / Q000235:genetics; D017209:Apoptosis / Q000235:genetics; D001120:Arginine / Q000235:genetics / Q000378:metabolism*; D001665:Binding Sites; D003593:Cytoplasm / Q000378:metabolism; D003598:Cytoskeletal Proteins / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D011110:Polymorphism, Genetic; D011392:Proline / Q000235:genetics / Q000378:metabolism*; D011485:Protein Binding; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism*; D018909:src Homology Domains / Q000235:genetics
chemical_list: D048868:Adaptor Proteins, Signal Transducing; C114545:CD2-associated protein; D003598:Cytoskeletal Proteins; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53; D001120:Arginine; D011392:Proline
keywords: CD2AP; P72R; SH3 domains; p53 polymorphism; polyproline