Integrative genomic approaches identify IKBKE as a breast cancer oncogene.

The karyotypic chaos exhibited by human epithelial cancers complicates efforts to identify mutations critical for malignant transformation. Here we integrate complementary genomic approaches to identify human oncogenes. We show that activation of the ERK and phosphatidylinositol 3-kinase (PI3K) signaling pathways cooperate to transform human cells.

The Cdk1 complex plays a prime role in regulating N-myc phosphorylation and turnover in neural precursors.

Myc family transcription factors are destabilized by phosphorylation of a conserved amino-terminal GSK-3beta motif. In proliferating cerebellar granule neuron precursors (CGNPs), Sonic hedgehog signaling induces N-myc expression, and N-myc protein is stabilized by insulin-like growth factor-mediated suppression of GSK-3beta. N-myc phosphorylation-mediated degradation is a prerequisite for CGNP growth arrest and differentiation.