14-3-3 suppresses the nuclear localization of threonine 157-phosphorylated p27Kip1
AUTOR(ES)
Sekimoto, Toshihiro
FONTE
Nature Publishing Group
RESUMO
p27Kip1 (p27), a CDK inhibitor, migrates into the nucleus, where it controls cyclin–CDK complex activity for proper cell cycle progression. We report here that the classical bipartite-type basic amino-acid cluster and the two downstream amino acids of the C-terminal region of p27 function as a nuclear localization signal (NLS) for its full nuclear import activity. Importin α3 and α5, but not α1, transported p27 into the nucleus in conjunction with importin β, as evidenced by an in vitro transport assay. It is known that Akt phosphorylates Thr 157 of p27 and this reduces the nuclear import activity of p27. Using a pull-down experiment, 14-3-3 was identified as the Thr157-phosphorylated p27NLS-binding protein. Although importin α5 bound to Thr157-phosphorylated p27NLS, 14-3-3 competed with importin α5 for binding to it. Thus, 14-3-3 sequestered phosphorylated p27NLS from importin α binding, resulting in cytoplasmic localization of NLS-phosphorylated p27. These findings indicate that 14-3-3 suppresses importin α/β-dependent nuclear localization of Thr157-phosphorylated p27, suggesting implications for cell cycle disorder in Akt-activated cancer cells.
ACESSO AO ARTIGO
http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=404318Documentos Relacionados
- p27Kip1 is expressed in proliferating cells in its form phosphorylated on threonine 187
- Involvement of 14-3-3 proteins in nuclear localization of telomerase
- Phosphorylated Nitrate Reductase and 14-3-3 Proteins1 : Site of Interaction, Effects of Ions, and Evidence for an AMP-Binding Site on 14-3-3 Proteins
- Binding of 14-3-3 proteins and nuclear export control the intracellular localization of the mitotic inducer Cdc25
- CRM1/Ran-Mediated Nuclear Export of p27Kip1 Involves a Nuclear Export Signal and Links p27 Export and Proteolysis