Switches.ELM

Switch #:

SWTI000661

Switch type:
Binary

Switch subtype:
Physicochemical compatibility

Description:
Phosphorylation of T205 in the Pin1-binding motif of F-box/WD repeat-containing protein 7 (FBXW7) induces binding to the Peptidyl-prolyl cis-trans isomerase NIMA-interacting 1 (PIN1) protein. Pin1 interacts with Fbw7 in a phoshorylation-dependent manner and promotes Fbw7 self-ubiquitination and protein degradation by disrupting Fbw7 dimerization. Paper also shows the over-expression of Pin1 suppresses the ability of Fbw7 to inhibit cell transformation and proliferation, suggesting a link between Pin1 overexpression and cancer.

Participants:
(1) F-box/WD repeat-containing protein 7 (FBXW7)
(2) Peptidyl-prolyl cis-trans isomerase NIMA-interacting 1 (PIN1)

Interactions

Interaction #1 FBXW7 - PIN1

Interfaces
(1) DOC_WW_Pin1_4 motif (₂₀₂CSATPT₂₀₇) in F-box/WD repeat-containing protein 7 (FBXW7)
(2) WW domain_(7-37) in Peptidyl-prolyl cis-trans isomerase NIMA-interacting 1 (PIN1)

Interaction Regulation
PTM-dependent Induction (Phosphorylation of T₂₀₅ on F-box/WD repeat-containing protein 7 (FBXW7)) of the F-box/WD repeat-containing protein 7 (FBXW7) DOC_WW_Pin1_4 motif - Peptidyl-prolyl cis-trans isomerase NIMA-interacting 1 (PIN1) WW domain interaction

Context

Switch localisation
ELM curated: nucleus, cytosol

Inferred: nucleoplasm

References

(1) Negative regulation of the stability and tumor suppressor function of fbw7 by the pin1 prolyl isomerase.
Min et al. Mol. Cell (2012)