Switch #: SWTI000313

Switch type: Pre-assembly

Switch subtype: Composite binding site formation

Description:
Binding of Cyclin-dependent kinase inhibitor 1C (CDKN1C) (p57) to the SCF-Skp2 ubiquitin ligase complex requires phosphorylation of p57 (CDKN1C) at T310, and association of the F-box protein S-phase kinase-associated protein 2 (SKP2) with the regulatory Cyclin-dependent kinases regulatory subunit 1 (CKS1B). SKP2 and CKS1B together generate a composite binding site for p57 (CDKN1C).

Participants:
(1) Cyclin-dependent kinases regulatory subunit 1 (CKS1B)
(2) S-phase kinase-associated protein 2 (SKP2)
(3) Cyclin-dependent kinase inhibitor 1C (CDKN1C)
(4) Cyclin-dependent kinase 2 (CDK2)

This is a sequential switch. The interactions in this switch take place in a defined order. The order is defined by numbers to the left of each interaction. More than one interaction can occur in each step, these interactions occur independently but are necessary for future step

1Interaction #1 CKS1B - SKP2

Interfaces
(1) Cyclin-dependent kinase regulatory subunit in Cyclin-dependent kinases regulatory subunit 1 (CKS1B)
(2) Leucine rich repeat _(205-229) and _(230-254) and _(255-284) and _(309-334) and _(335-359) in S-phase kinase-associated protein 2 (SKP2)

1Interaction #2 CDKN1C - CDK2

Interfaces
(3) MOD_CDK_1 motif (₃₀₇VEQTPRK₃₁₃) in Cyclin-dependent kinase inhibitor 1C (CDKN1C)
(4) Protein kinase domain _(4-286) in Cyclin-dependent kinase 2 (CDK2)

2Interaction #3 CDKN1C - Interaction #1 CKS1B - SKP2

Requires Interaction #1 CKS1B - SKP2
Requires Interaction #2 CDKN1C - CDK2

Interfaces
(5) DEG_SCF_SKP2-CKS1_1 motif (₃₀₆SVEQTPRK₃₁₃) in Cyclin-dependent kinase inhibitor 1C (CDKN1C)
(6) Interaction #1 CKS1B - SKP2

Interaction Regulation
PTM-dependent Induction (Phosphorylation of T₃₁₀ on Cyclin-dependent kinase inhibitor 1C (CDKN1C)) of the Cyclin-dependent kinase inhibitor 1C (CDKN1C) DEG_SCF_SKP2-CKS1_1 motif - interaction

Regulatory Enzymes for switch
Modifying enzymes for residue: T₃₁₀: Cyclin-dependent kinase 2 (CDK2)

(1) Degradation of p57Kip2 mediated by SCFSkp2-dependent ubiquitylation.
Kamura et al. Proc. Natl. Acad. Sci. U.S.A. (2003)

Other switches involving participants
Cyclin-dependent kinases regulatory subunit 1 (CKS1B) - 1 more (view)
S-phase kinase-associated protein 2 (SKP2) - 3 more (view)
Cyclin-dependent kinase 2 (CDK2) - 1 more (view)

Other switches involving interfaces
Protein kinase domain - 35 more (view)
Cyclin-dependent kinase regulatory subunit - 2 more (view)
Leucine rich repeat - 2 more (view)
MOD_CDK_1 - 3 more (view)
DEG_SCF_SKP2-CKS1_1 - 2 more (view)