title: A novel site of AKT-mediated phosphorylation in the human MDM2 onco-protein.
abstract: MDM2 is an E3 ubiquitin ligase which mediates ubiquitylation and proteasome-dependent degradation of the p53 tumor suppressor protein. Phosphorylation of MDM2 by the protein kinase AKT is thought to regulate MDM2 function in response to survival signals, but there has been uncertainty concerning the identity of the sites phosphorylated by AKT. In the present study, we identify Ser-166, a site previously reported as an AKT target, and Ser-188, a novel site which is the major site of phosphorylation of MDM2 by AKT in vitro. Analysis of MDM2 in cultured cells confirms that Ser-166 and Ser-188 are phosphorylated by AKT in a physiological context.
authors.affiliation: Molecular Signaling Group, Biomedical Research Centre, University of Dundee, Dundee DD1 9SY, UK.
authors.forename: Diane
authors.initials: D
authors.lastname: Milne
authors.forename: Petros
authors.initials: P
authors.lastname: Kampanis
authors.forename: Samantha
authors.initials: S
authors.lastname: Nicol
authors.forename: Sylvia
authors.initials: S
authors.lastname: Dias
authors.forename: David G
authors.initials: DG
authors.lastname: Campbell
authors.forename: Frances
authors.initials: F
authors.lastname: Fuller-Pace
authors.forename: David
authors.initials: D
authors.lastname: Meek
mesh_terms: D000595:Amino Acid Sequence; D001769:Blood; D045744:Cell Line, Tumor; D002852:Chromatography, Ion Exchange; D006801:Humans; D016297:Mutagenesis, Site-Directed; D009687:Nuclear Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D010766:Phosphorylation; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D011518:Proto-Oncogene Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D051057:Proto-Oncogene Proteins c-akt; D051736:Proto-Oncogene Proteins c-mdm2; D012694:Serine / Q000378:metabolism
chemical_list: D009687:Nuclear Proteins; D011518:Proto-Oncogene Proteins; D012694:Serine; C497206:MDM2 protein, human; D051736:Proto-Oncogene Proteins c-mdm2; C494918:AKT1 protein, human; D017346:Protein Serine-Threonine Kinases; D051057:Proto-Oncogene Proteins c-akt