Yet, there is a striking similarity between intermolecular auto-phosphorylation of protein kinases and auto-ubiquitination that results in self-activation or self-inhibition of E3 ligases.
Auto-ubiquitination of Itch ligase was shown to be an intermolecular reaction, which generated K63-linkages, rather than the K48-linked chains that target Itch for proteasomal degradation [26].