Switch #:
SWTI000678
Switch type:
Specificity
Switch subtype:
Competition

Description:
The transcriptional coactivator YAP1 and the ubiquitin ligase Itch competitively bind to the same WW-binding motif of p73. Binding of YAP1 prevents Itch-mediated ubiquitylation of p73, resulting in stabilisation, and increases trancriptional activity of p73.

Participants:
(1) Tumor protein p73 (TP73)
(2) Yorkie homolog (YAP1)
(3) E3 ubiquitin-protein ligase Itchy homolog (ITCH)

Interactions
Interaction #1 TP73 - YAP1

Is mutually exclusive with Interaction #2 TP73 - ITCH

Interfaces
(1) LIG_WW_1 motif (484PPPY487) in Tumor protein p73 (TP73)
(2) WW domain (173-202) and (232-261) in Yorkie homolog (YAP1)

Interaction Regulation
Effector binding Inhibition (E3 ubiquitin-protein ligase Itchy homolog (ITCH)) of the Tumor protein p73 (TP73) LIG_WW_1 motif - Yorkie homolog (YAP1) WW domain interaction

Interaction #2 TP73 - ITCH

Is mutually exclusive with Interaction #1 TP73 - YAP1

Interfaces
(3) LIG_WW_1 motif (484PPPY487) in Tumor protein p73 (TP73)
(4) WW domain (328-357) and (360-389) and (440-469) and (480-509) in E3 ubiquitin-protein ligase Itchy homolog (ITCH)

Interaction Regulation
Effector binding Inhibition (Yorkie homolog (YAP1)) of the Tumor protein p73 (TP73) LIG_WW_1 motif - E3 ubiquitin-protein ligase Itchy homolog (ITCH) WW domain interaction

Context
Switch localisation
ELM curated: cytosol, integral membrane protein, integral plasma membrane protein
Inferred: cytosol, transcription factor complex
References

(1) The Yes-associated protein 1 stabilizes p73 by preventing Itch-mediated ubiquitination of p73.
Levy et al. Cell Death Differ. (2007)




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