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).
Rossi, M, De Laurenzi, V, Munarriz, E, Green, DR, Liu, YC, Vousden, KH, Cesareni, G, Melino, G
Levy, D, Reuven, N, Shaul, Y
ubiquitin protein ligase activity of ITCH [cytosol]
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