Switch #:
SWTI000695
Switch type:
Binary
Switch subtype:
Physicochemical compatibility

Description:
Phosphorylation of S146 in the PCNA-binding motif of Cyclin-dependent kinase inhibitor 1 (CDKN1A) by PKC subfamily inhibits binding to Proliferating cell nuclear antigen (PCNA). As a result, Cyclin-dependent kinase inhibitor 1 (CDKN1A) no longer inhibits Proliferating cell nuclear antigen (PCNA) and blocking of DNA replication is relieved.

Participants:
(1) Cyclin-dependent kinase inhibitor 1 (CDKN1A)
(2) Proliferating cell nuclear antigen (PCNA)

Interactions
Interaction #1 CDKN1A - PCNA

Interfaces
(1) LIG_PCNA_PIPBox_1 motif (144QTSMTDFYHS153) in Cyclin-dependent kinase inhibitor 1 (CDKN1A)
(2) Proliferating cell nuclear antigen, C-terminal domain (127-254) in Proliferating cell nuclear antigen (PCNA)

Interaction Regulation
PTM-dependent Inhibition (Phosphorylation of S146 on Cyclin-dependent kinase inhibitor 1 (CDKN1A)) of the Cyclin-dependent kinase inhibitor 1 (CDKN1A) LIG_PCNA_PIPBox_1 motif - Proliferating cell nuclear antigen (PCNA) Proliferating cell nuclear antigen, C-terminal domain interaction

Regulatory Enzymes for switch
Modifying enzymes for residue: S146: PKC subfamily

Inferred Regulatory Enzymes for switch
Putative modifying enzymes for residue: S146 : PKB_group, RAC-alpha serine/threonine-protein kinase (AKT1), Serine/threonine-protein kinase pim-2 (PIM2), Protein kinase C alpha type (PRKCA), Serine/threonine-protein kinase pim-1 (PIM1).

Context
Switch localisation
Curated: PCNA-p21 complex, nucleus
ELM curated: nucleus
Inferred: PCNA-p21 complex, nucleoplasm

Switch cell cycle phase
Curated: mitotic S phase
References

(1) Reversible phosphorylation at the C-terminal regulatory domain of p21(Waf1/Cip1) modulates proliferating cell nuclear antigen binding.
Scott et al. J. Biol. Chem. (2000)




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