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Switch #:
SWTI000694
Switch type:
Binary
Switch subtype:
Physicochemical compatibility

Description:
Phosphorylation of T145 in the PCNA-binding motif of Cyclin-dependent kinase inhibitor 1 (CDKN1A) by RAC-alpha serine/threonine-protein kinase (AKT1) 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 T145 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: T145: RAC-alpha serine/threonine-protein kinase (AKT1)

Inferred Regulatory Enzymes for switch
Putative modifying enzymes for residue: T145 : PKB_group, Protein kinase C alpha type (PRKCA), RAC-alpha serine/threonine-protein kinase (AKT1), Death-associated protein kinase 3 (DAPK3), Serine/threonine-protein kinase pim-2 (PIM2), 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

Switch pathways
Curated: Cell cycle
References

(1) Akt-dependent phosphorylation of p21(Cip1) regulates PCNA binding and proliferation of endothelial cells.
Rössig et al. Mol. Cell. Biol. (2001)

See also

Other switches involving participants
Cyclin-dependent kinase inhibitor 1 (CDKN1A) - 2 more (view)
Proliferating cell nuclear antigen (PCNA) - 3 more (view)

Other switches involving interfaces
Proliferating cell nuclear antigen, C-terminal domain - 3 more (view)
LIG_PCNA_PIPBox_1 - 2 more (view)


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