Switch #:
SWTI000339
Switch type:
Specificity
Switch subtype:
Competition

Description:
The docking sites for PP1 (e.g. Serine/threonine-protein phosphatase PP1-alpha catalytic subunit (PPP1CA)) and Cdk-Cyclins (e.g. Cyclin-A2 (CCNA2)) on Retinoblastoma-associated protein (RB1) overlap, which makes their binding to RB1 mutually exclusive. Hypophosphorylated RB1 blocks E2F-dependent transcription, while hyperphosphorylation inactivates RB1 as a repressor, thereby promoting cell cycle progression.

Participants:
(1) Retinoblastoma-associated protein (RB1)
(2) Cyclin-A2 (CCNA2)
(3) Serine/threonine-protein phosphatase PP1-alpha catalytic subunit (PPP1CA)

Interactions
Interaction #1 RB1 - CCNA2

Is mutually exclusive with Interaction #2 RB1 - PPP1CA

Interfaces
(1) DOC_CYCLIN_1 motif (873KKLRF877) in Retinoblastoma-associated protein (RB1)
(2) Cyclin, N-terminal domain (181-307) in Cyclin-A2 (CCNA2)

Interaction Regulation
Effector binding Inhibition (Serine/threonine-protein phosphatase PP1-alpha catalytic subunit (PPP1CA)) of the Retinoblastoma-associated protein (RB1) DOC_CYCLIN_1 motif - Cyclin-A2 (CCNA2) Cyclin, N-terminal domain interaction

Additional Information
Affinity : 6.3 µM
Interaction #2 RB1 - PPP1CA

Is mutually exclusive with Interaction #1 RB1 - CCNA2

Interfaces
(3) DOC_PP1 motif (872LKKLRFD878) in Retinoblastoma-associated protein (RB1)
(4) Calcineurin-like phosphoesterase (57-252) in Serine/threonine-protein phosphatase PP1-alpha catalytic subunit (PPP1CA)

Interaction Regulation
Effector binding Inhibition (Cyclin-A2 (CCNA2)) of the Retinoblastoma-associated protein (RB1) DOC_PP1 motif - Serine/threonine-protein phosphatase PP1-alpha catalytic subunit (PPP1CA) Calcineurin-like phosphoesterase interaction

Additional Information
Affinity : 2.1 µM
Structural information: 3N5U
Context
References

(1) An overlapping kinase and phosphatase docking site regulates activity of the retinoblastoma protein.
Hirschi et al. Nat. Struct. Mol. Biol. (2010)




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