The AAK/PLK1 axis in HRLs. AAK and PLK1 directly, or indirectly, regulate the stability of oncogenes (eg, c-myc, Notch) and tumor suppressors (eg, p53) implicated in the pathogenesis of most HRLs. Schematic representations of posttranslational phosphorylation (Y) and ubiquitination (Ub) modifications are indicated (blue arrows), as are inhibitory modifications (red bars). Tumor suppressors that are recurrently deleted in many HRLs are indicated in red. Transcription factors promoting c-myc or PLK1 expression are shown (green arrows). β-Trcp, β-transducin repeat-containing protein; CAMKIIγ, calcium/calmodulin-dependent kinase II γ; GSK3, glycogen synthase kinase 3; Mdm2, mouse double minute 2 homolog; mTOR, mammalian target of rapamycin; p14ARF, p14 alternative reading frame; PDK1, phosphoinositide-dependent kinase 1; PI3K, phosphatidylinositol 3-kinase; Pin1, peptidylprolyl cis/trans isomerase, NIMA-interacting 1; PIP2, phosphatidylinositol 4,5-bisphosphate; PIP3, phosphatidylinositol (3,4,5)-trisphosphate; PP2A, protein phosphatase 2A; PTEN, phosphatase and tensin homolog.