Switch #: SWTI000692

Switch type: Specificity

Switch subtype: Motif hiding

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)

Other switches involving participants
Cyclin-dependent kinase inhibitor 1B (CDKN1B) - 4 more (view)
Importin subunit alpha-1 (KPNA1) - 9 more (view)
14-3-3 protein gamma (YWHAG) - 1 more (view)

Other switches involving interfaces
LIG_14-3-3_3 - 16 more (view)
14-3-3 protein - 38 more (view)
Armadillo/beta-catenin-like repeat - 16 more (view)
ELM:TRG_NLS - 1 more (view)