SETDB1 and non-small cell lung carcinoma: In NSCLC, SETDB1 triggers di- and tri-methylation of the AKT K64 site followed by initiation of K63-linked AKT ubiquitination by recruiting Jumonji Domain-Containing Protein 2A (JMJD2A) and E3 ligases (e.g., TRAF6 and Skp2-SCF) to the AKT complex, which in turn leads to cell membrane recruitment, T308 phosphorylation and subsequently activation of AKT.