title: Proteomics of p53 in diagnostics and therapy of acute myeloid leukemia.
abstract: The anti-oncogene TP53 is frequently mutated in human cancer, but in hematological malignancies this is a rare feature. In acute myeloid leukemia (AML) more than 90% of the patients comprise wild type TP53 in their cancer cells, but if TP53 is mutated or deleted the disease is often found to be chemoresistant. In this review we define proteomics of the oncogene product p53 as the study of proteins in the p53 regulating signaling networks, as well as the protein study of members of the p53 family itself. Various messenger RNA splice forms as well as a multitude of post-translational modifications give a high number of protein isoforms in the p53 family. Some of the proteomic techniques allow detection of various isoforms, such as two-dimensional gel electrophoresis in combination with tandem mass spectrometry (MS/MS) and this methodology may therefore increasingly be used as a diagnostic tool in human disease. We introduce the p53 protein as an illustration of the complexity of post-translational modifications that may affect one highly connected protein and discuss the possible impact in AML diagnostics if the p53 profile is reflecting cell stress and status of signal transduction systems of the malignancy.
authors.affiliation: Institute of Medicine, Hematology Section, University of Bergen, Haukeland University Hospital, N-5021 Bergen, Norway.
authors.forename: Nina
authors.initials: N
authors.lastname: Anensen
authors.forename: Ingvild
authors.initials: I
authors.lastname: Haaland
authors.forename: Clive
authors.initials: C
authors.lastname: D'Santos
authors.forename: Werner
authors.initials: W
authors.lastname: Van Belle
authors.forename: Bjørn Tore
authors.initials: BT
authors.lastname: Gjertsen
mesh_terms: D000107:Acetylation; D000208:Acute Disease; D006801:Humans; D007951:Leukemia, Myeloid / Q000175:diagnosis / Q000378:metabolism / Q000628:therapy; D009154:Mutation; D010766:Phosphorylation; D040901:Proteomics / Q000379:methods; D015398:Signal Transduction; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism; D014452:Ubiquitins / Q000378:metabolism
chemical_list: D016159:Tumor Suppressor Protein p53; D014452:Ubiquitins