title: Altered phosphorylation and oligomerization of p53 in adenovirus type 12-transformed cells.
abstract: Loss of function of the tumor-suppressor protein p53 is, in general, either caused by mutation, inducing a conformational change, or by binding to inactivating cellular (e.g. MDM2) or viral (e.g. SV40 large T) proteins. In adenovirus type 12 (Ad12)-transformed cells, p53 is stabilized without detectable binding to the Ad12 E1B/54 kDa protein and still present in a wild-type conformation but contains a mutant-like activity in cellular transformation. In this study we examined whether the changed characteristics of p53 in Ad12-transformed cells are correlated with changes in phosphorylation or complex formation of the protein. By making tryptic phosphopeptide maps we found a significant increase in the phosphorylation of the N-terminus of p53. Furthermore, expression of E1A was found to be essential for the altered phosphorylation, while expression of only Ad12 E1B/54 kDa is sufficient to increase the protein half-life. Additionally, we observed p53 to be present in increased molecular weight complexes in Ad12-transformed cells. We conclude that both the phosphorylation and oligomerization of p53 is changed as a result of Ad12 transformation.
authors.affiliation: Sylvius Laboratories, Leiden University, The Netherlands.
authors.forename: W T
authors.initials: WT
authors.lastname: Steegenga
authors.forename: A
authors.initials: A
authors.lastname: Shvarts
authors.forename: T
authors.initials: T
authors.lastname: van Laar
authors.forename: A J
authors.initials: AJ
authors.lastname: van der Eb
authors.forename: A G
authors.initials: AG
authors.lastname: Jochemsen
mesh_terms: D000256:Adenoviridae / Q000502:physiology*; D017501:Adenovirus E1B Proteins / Q000235:genetics; D001704:Biopolymers; D002472:Cell Transformation, Viral; D002478:Cells, Cultured; D006801:Humans; D010710:Phosphates / Q000378:metabolism; D010766:Phosphorylation; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*
chemical_list: D017501:Adenovirus E1B Proteins; D001704:Biopolymers; D010710:Phosphates; D016159:Tumor Suppressor Protein p53