Fiche publication
Date publication
mars 2021
Journal
Nature communications
Auteurs
Membres identifiés du Cancéropôle Est :
Dr TRAVE Gilles
,
Mr EBERLING Pascal
,
Dr GOGL Gergo
Tous les auteurs :
Gogl G, Tugaeva KV, Eberling P, Kostmann C, Trave G, Sluchanko NN
Lien Pubmed
Résumé
The seven 14-3-3 isoforms are highly abundant human proteins encoded by similar yet distinct genes. 14-3-3 proteins recognize phosphorylated motifs within numerous human and viral proteins. Here, we analyze by X-ray crystallography, fluorescence polarization, mutagenesis and fusicoccin-mediated modulation the structural basis and druggability of 14-3-3 binding to four E6 oncoproteins of tumorigenic human papillomaviruses. 14-3-3 isoforms bind variant and mutated phospho-motifs of E6 and unrelated protein RSK1 with different affinities, albeit following an ordered affinity ranking with conserved relative K ratios. Remarkably, 14-3-3 isoforms obey the same hierarchy when binding to most of their established targets, as supported by literature and a recent human complexome map. This knowledge allows predicting proportions of 14-3-3 isoforms engaged with phosphoproteins in various tissues. Notwithstanding their individual functions, cellular concentrations of 14-3-3 may be collectively adjusted to buffer the strongest phosphorylation outbursts, explaining their expression variations in different tissues and tumors.
Référence
Nat Commun. 2021 03 15;12(1):1677
