ITCH polyubiquitinates TP73

Stable Identifier
Reaction [transition]
Homo sapiens
Locations in the PathwayBrowser
SVG |   | PPTX  | SBGN
Click the image above or here to open this reaction in the Pathway Browser
The layout of this reaction may differ from that in the pathway view due to the constraints in pathway layout

The E3 ubiquitin-protein ligase ITCH polyubiquitinates TP73 (p73), targeting it for degradation. In response to DNA damage, ITCH levels are downregulated, allowing TP73 to accumulate (Rossi et al. 2005). Downregulation of ITCH in response to DNA damage is the consequence of DNA damage-induced phosphorylation of YAP1 by ABL1. YAP1 phosphorylated by ABL1 is no longer able to bind to RUNX1, and the complex of RUNX1 and YAP1 is needed for transcription of the ITCH gene (Levy, Reuven and Shaul 2008).

Literature References
PubMed ID Title Journal Year
18701449 A regulatory circuit controlling Itch-mediated p73 degradation by Runx

Shaul, Y, Reuven, N, Levy, D

J. Biol. Chem. 2008
15678106 The ubiquitin-protein ligase Itch regulates p73 stability

Cesareni, G, Melino, G, Liu, YC, Green, DR, Munarriz, E, Rossi, M, Vousden, KH, De Laurenzi, V

EMBO J. 2005
Catalyst Activity

ubiquitin protein ligase activity of ITCH [cytosol]

Orthologous Events
Cite Us!