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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)

Interactions
Interaction #2 CDKN1B - YWHAG

Interfaces
(3) LIG_14-3-3_3 motif (154159) in Cyclin-dependent kinase inhibitor 1B (CDKN1B)
(4) 14-3-3 protein (4-241) in 14-3-3 protein gamma (YWHAG)

Interaction Regulation
PTM-dependent Induction (Phosphorylation of T157 on Cyclin-dependent kinase inhibitor 1B (CDKN1B)) of the Cyclin-dependent kinase inhibitor 1B (CDKN1B) LIG_14-3-3_3 motif - 14-3-3 protein gamma (YWHAG) 14-3-3 protein interaction

Regulatory Enzymes for switch
Modifying enzymes for residue: T157: RAC-alpha serine/threonine-protein kinase (AKT1)

Context
References

(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)

See also

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)




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