Skp2 S256 phosphorylation by AMPK promotes Skp2-SCF complex formation enhancing its E3 ligase activation, which leads to K63-ubiquitination and activation of Akt, and finally contributing to a resistance to EGFR targeting therapy, such as Gefitinib, in non-small cell lung cancer cells (NSCLC) [57]. The gene discussed is EGFR; the disease is non-small cell lung carcinoma.