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Switch #:
SWTI000457
Switch type:
Cumulative
Switch subtype:
Rheostatic

Description:
Multisite phosphorylation of S15 and T18 and S20 and S33 and S37 and S46 in the TAD region of Cellular tumor antigen p53 (TP53) additively enhances its affinity for CREB-binding protein (CREBBP).

Participants:
(1) Cellular tumor antigen p53 (TP53)
(2) CREB-binding protein (CREBBP)

Interactions
Interaction #1 TP53 - CREBBP

Interfaces
(1) ELM:LIG_TAZ2 motif (19FSDLWKL25) in Cellular tumor antigen p53 (TP53)
(2) TAZ zinc finger (1770-1843) in CREB-binding protein (CREBBP)

Interaction Regulation
PTM-dependent Enhancement (Phosphorylation of S15, T18, S20, S33, S37 and S46 on Cellular tumor antigen p53 (TP53)) of the Cellular tumor antigen p53 (TP53) LIG_TAZ2 motif - CREB-binding protein (CREBBP) TAZ zinc finger interaction

Inferred Regulatory Enzymes for switch
Putative modifying enzymes for residue: S15 : Serine-protein kinase ATM (ATM), Serine-protein kinase ATM (Atm), ATM, Serine/threonine-protein kinase ATR (ATR), Cyclin-dependent kinase 5 (CDK5), Serine/threonine-protein kinase Chk1 (CHEK1), Serine/threonine-protein kinase Chk2 (CHEK2), Dual specificity tyrosine-phosphorylation-regulated kinase 1A (DYRK1A), Mitogen-activated protein kinase 3 (MAPK3), Mitogen-activated protein kinase 1 (MAPK1), Mitogen-activated protein kinase 1 (Mapk1), Serine/threonine-protein kinase STK11 (STK11), NUAK family SNF1-like kinase 1 (NUAK1), TP53-regulating kinase (TP53RK), Serine/threonine-protein kinase SMG1 (SMG1), Mitogen-activated protein kinase 14 (MAPK14), DNA-dependent protein kinase catalytic subunit (PRKDC). T18 : CK1_group, Dual specificity protein kinase TTK (TTK), 5'-AMP-activated protein kinase catalytic subunit alpha-1 (PRKAA1), Casein kinase I isoform alpha (CSNK1A1), Casein kinase I isoform delta (CSNK1D), Serine/threonine-protein kinase Chk1 (CHEK1), Serine/threonine-protein kinase Chk2 (CHEK2), Death-associated protein kinase 1 (DAPK1), DNA-dependent protein kinase catalytic subunit (PRKDC), Serine/threonine-protein kinase VRK1 (VRK1). S20 : 5'-AMP-activated protein kinase catalytic subunit alpha-1 (PRKAA1), ATM, Cyclin-dependent kinase 5 (CDK5), Casein kinase I isoform alpha (CSNK1A1), Casein kinase I isoform delta (CSNK1D), Death-associated protein kinase 3 (DAPK3), DNA-dependent protein kinase catalytic subunit (PRKDC), Serine/threonine-protein kinase 17A (STK17A), Mitogen-activated protein kinase 8 (MAPK8), Mitogen-activated protein kinase 9 (MAPK9), MAP kinase-activated protein kinase 2 (MAPKAPK2), Serine/threonine-protein kinase PLK3 (PLK3), Serine/threonine-protein kinase Chk1 (CHEK1), Serine/threonine-protein kinase Chk2 (CHEK2), Death-associated protein kinase 1 (DAPK1). S33 : CDK_group, GSK-3_group, Cyclin-dependent kinase 5 (CDK5), Cyclin-dependent kinase 9 (CDK9), Mitogen-activated protein kinase 14 (MAPK14), Cyclin-dependent kinase 7 (CDK7). S37 : Serine/threonine-protein kinase ATR (ATR), Serine/threonine-protein kinase Chk1 (CHEK1), Serine/threonine-protein kinase Chk2 (CHEK2), MAP kinase-activated protein kinase 5 (MAPKAPK5), DNA-dependent protein kinase catalytic subunit (PRKDC). S46 : Serine-protein kinase ATM (ATM), ATM, Cyclin-dependent kinase 5 (CDK5), DNA-dependent protein kinase catalytic subunit (PRKDC), Protein kinase C delta type (PRKCD), Mitogen-activated protein kinase 14 (MAPK14), Dual specificity tyrosine-phosphorylation-regulated kinase 2 (DYRK2), Homeodomain-interacting protein kinase 2 (HIPK2).

Additional Information
Affinity : p53(13-61): 0.02 µM, p53(13-57)pS15: 0.0068 µM, p53(13-57)pT18: 0.0065 µM, p53(13-57)pS20: 0.0053 µM, p53(13-57)pS33: 0.0094 µM, p53(13-57)pS37: 0.014 µM, p53(13-57)pS46: 0.0078 µM, p53(13-57)pS15pT18: 0.0025 µM, p53(13-57)pS15pS20: 0.0012 µM, p53(13-57)pT18pS20: 0.0025 µM, p53(13-57)pS15pT18pS20: 0.0009 µM, p53(13-61)pS33pS37: 0.0020 µM, p53(13-61)pS33pS46: 0.0014 µM, p53(13-61)pS33pS37pS46: 0.0007 µM
Structural information: 2K8F
Context
Switch localisation
Curated: nuclear chromatin, nucleus
Inferred: cytoplasm, nuclear chromatin

Switch cell cycle phase
Curated: mitotic G1 DNA damage checkpoint

Switch pathways
Curated: Cell cycle, G1/S DNA Damage Checkpoints
Inferred: Wnt signaling pathway
References

(1) Graded enhancement of p53 binding to CREB-binding protein (CBP) by multisite phosphorylation.
Lee et al. Proc. Natl. Acad. Sci. U.S.A. (2010)

(2) Structural basis for p300 Taz2-p53 TAD1 binding and modulation by phosphorylation.
Feng et al. Structure (2009)

See also

Other switches involving participants
Cellular tumor antigen p53 (TP53) - 10 more (view)

Other switches involving interfaces
TAZ zinc finger - 1 more (view)


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