Reactome | ITCH polyubiquitinates TP73

ITCH polyubiquitinates TP73

Stable Identifier

R-HSA-8956684

Type

Reaction [transition]

Species

Homo sapiens

Compartment

cytosol

ReviewStatus

5/5

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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 Levy, D, Reuven, N, Shaul, Y	J. Biol. Chem.	2008
15678106	The ubiquitin-protein ligase Itch regulates p73 stability Rossi, M, De Laurenzi, V, Munarriz, E, Green, DR, Liu, YC, Vousden, KH, Cesareni, G, Melino, G	EMBO J.	2005