Description: Phosphorylation of a 14-3-3-binding motif in the NLS of Cyclin-dependent kinase inhibitor 1B (CDKN1B) by RAC-alpha serine/threonine-protein kinase (AKT1) induces binding of 14-3-3 protein gamma (YWHAG), which hides the NLS and prevents binding to Importin subunit alpha-1 (KPNA1), thereby mediating cytoplasmic retention of Cyclin-dependent kinase inhibitor 1B (CDKN1B). Binding of 14-3-3 dimer involves an additional C-terminal 14-3-3-binding motif (see switch details).
Participants: (1) Cyclin-dependent kinase inhibitor 1B (CDKN1B) (2) Importin subunit alpha-1 (KPNA1) (3) 14-3-3 protein gamma (YWHAG)
(1) PKB/Akt mediates cell-cycle progression by phosphorylation of p27(Kip1) at threonine 157 and modulation of its cellular localization.Shin et al. Nat. Med. (2002) (2) Cytoplasmic relocalization and inhibition of the cyclin-dependent kinase inhibitor p27(Kip1) by PKB/Akt-mediated phosphorylation in breast cancer.Viglietto et al. Nat. Med. (2002) (3) 14-3-3 suppresses the nuclear localization of threonine 157-phosphorylated p27(Kip1).Sekimoto et al. EMBO J. (2004)
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