title: Activation of p53 by conjugation to the ubiquitin-like protein SUMO-1.
abstract: The growth-suppressive properties of p53 are controlled by posttranslational modifications and by regulation of its turnover rate. Here we show that p53 can be modified in vitro and in vivo by conjugation to the small ubiquitin-like protein SUMO-1. A lysine residue at amino acid position 386 of p53 is required for this previously undescribed modification, strongly suggesting that this lysine residue serves as the major attachment site for SUMO-1. Unlike ubiquitin, attachment of SUMO-1 does not appear to target proteins for rapid degradation but rather, has been proposed to change the ability of the modified protein to interact with other cellular proteins. Accordingly, we provide evidence that conjugation of SUMO-1 to wild-type p53 results in an increased transactivation ability of p53. We suggest that posttranslational modification of p53 by SUMO-1 conjugation provides a novel mechanism to regulate p53 activity.
authors.affiliation: Laboratorio Nazionale, Consorzio Interuniversitario Biotecnologie, AREA Science Park, Padriciano 99, 34012 Trieste, Italy.
authors.forename: M
authors.initials: M
authors.lastname: Gostissa
authors.forename: A
authors.initials: A
authors.lastname: Hengstermann
authors.forename: V
authors.initials: V
authors.lastname: Fogal
authors.forename: P
authors.initials: P
authors.lastname: Sandy
authors.forename: S E
authors.initials: SE
authors.lastname: Schwarz
authors.forename: M
authors.initials: M
authors.lastname: Scheffner
authors.forename: G
authors.initials: G
authors.lastname: Del Sal
mesh_terms: D000595:Amino Acid Sequence; D019943:Amino Acid Substitution; D000818:Animals; D001665:Binding Sites; D002460:Cell Line; D006801:Humans; D007700:Kinetics; D008239:Lysine; D051379:Mice; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed; D011994:Recombinant Proteins / Q000737:chemistry / Q000378:metabolism; D025842:SUMO-1 Protein; D014162:Transfection; D014407:Tumor Cells, Cultured; D016159:Tumor Suppressor Protein p53 / Q000737:chemistry* / Q000378:metabolism*; D014452:Ubiquitins / Q000737:chemistry / Q000378:metabolism*
chemical_list: D011994:Recombinant Proteins; D025842:SUMO-1 Protein; D016159:Tumor Suppressor Protein p53; D014452:Ubiquitins; D008239:Lysine