title: Serine phosphorylation in the NH2 terminus of p53 facilitates transactivation.
abstract: Murine tumor suppressor p53 is phosphorylated in the NH2-terminal transactivating domain at serines 9, 18, and 37. Change of any one of these serines to either alanine or aspartic acid did not alter p53 suppression of transformation of rat embryo fibroblasts by activated ras and E1A. Change of any two of these serines to alanines, however, led to a significant decrease in suppressor function. Substitution of alanines for all three serines caused the most severe loss of suppression and also reduced transactivation functions. The triple substitution had no apparent effects on intracellular accumulation or localization of p53, oligomerization, DNA binding, or interaction with the TFIID TATA-binding protein. In contrast, triple substitution of aspartic acid for serines 9, 18, and 37 had minimal effects on suppression and transactivation by p53. These results argue strongly that phosphorylation of serines 9, 18, and 37 facilitates the suppression and transactivation functions of p53.
authors.affiliation: Department of Molecular Genetics and Microbiology, State University of New York, Stony Brook 11794, USA.
authors.forename: G A
authors.initials: GA
authors.lastname: Mayr
authors.forename: M
authors.initials: M
authors.lastname: Reed
authors.forename: P
authors.initials: P
authors.lastname: Wang
authors.forename: Y
authors.initials: Y
authors.lastname: Wang
authors.forename: J F
authors.initials: JF
authors.lastname: Schweds
authors.forename: P
authors.initials: P
authors.lastname: Tegtmeyer
mesh_terms: D000409:Alanine / Q000235:genetics / Q000378:metabolism; D000818:Animals; D001224:Aspartic Acid / Q000235:genetics / Q000378:metabolism; D001483:Base Sequence; D001665:Binding Sites; D002467:Cell Nucleus / Q000378:metabolism; D004247:DNA / Q000235:genetics / Q000378:metabolism; D015870:Gene Expression; D051379:Mice; D008969:Molecular Sequence Data; D009154:Mutation; D010766:Phosphorylation; D051381:Rats; D012680:Sensitivity and Specificity; D012694:Serine / Q000378:metabolism*; D015533:Transcriptional Activation / Q000502:physiology*; D014170:Transformation, Genetic / Q000502:physiology; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism*
chemical_list: D016159:Tumor Suppressor Protein p53; D001224:Aspartic Acid; D012694:Serine; D004247:DNA; D000409:Alanine