Papillomavirus binding factor (PBF)-mediated inhibition of cell growth is regulated by 14-3-3beta.
The cellular factor, papillomavirus (PV)-binding factor (PBF)/Huntington's disease binding protein 2 (HDBP2), was identified by its ability to bind regulatory sequences of certain papillomavirus types as well as the Huntington's disease gene. PBF is thought to be a novel nuclear-shuttling transcription factor with unknown function. To further characterize PBF, we identified 14-3-3beta as an interaction partner. We demonstrated that PBF binds to 14-3-3beta using two motifs. Akt-kinase and an unidentified kinase that are activated by the PI3K-signaling pathway were able to phosphorylate these motifs, allowing PBF to associate with 14-3-3beta. This interaction may contribute to the control of the subcellular localization of PBF, which migrated into the nucleus in the absence of growth factors. Over-expression of PBF resulted in the inhibition of cell growth, which was enhanced using a 14-3-3 binding-deficient PBF mutant. Thus, our experiments characterized PBF as a new cellular factor mediating the effects of PI3K/Akt signaling and 14-3-3 on cell growth.
Sichtig
Nadine
N
Institute of Virology, University of Cologne, Fürst-Pückler-Strasse 56, 50935 Cologne, Germany.
Silling
Steffi
S
Steger
Gertrud
G
D048948:14-3-3 Proteins / Q000378:metabolism / Q000502:physiology*; D021581:Active Transport, Cell Nucleus; D000595:Amino Acid Sequence; D002460:Cell Line; D002467:Cell Nucleus / Q000378:metabolism; D049109:Cell Proliferation; D004268:DNA-Binding Proteins / Q000378:metabolism / Q000502:physiology*; D006801:Humans; D008954:Models, Biological; D008969:Molecular Sequence Data; D027383:Papillomaviridae / Q000378:metabolism* / Q000502:physiology*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D010766:Phosphorylation; D025941:Protein Interaction Mapping; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism / Q000502:physiology*
D048948:14-3-3 Proteins; D004268:DNA-Binding Proteins; D014157:Transcription Factors; C484332:ZNF395 protein, human; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt