Schematic representation of SKP2-mediated regulation of p27 in BCR-ABL–positive cell lines. (A) BCR-ABL kinase activity induces expression of SKP2, which increases the activity of SCF^SKP2, which in turn promotes p27 degradation. This releases CDK2 from p27 inhibition and stimulates cell-cycle progression in BCR-ABL positive cell lines. In primary cells, BCR-ABL additionally promotes cytoplasmic localization of p27. (B) Inhibition of BCR-ABL kinase activity by imatinib decreases SKP2 expression, which leads to accumulation of pT187p27, which restores inhibition of CDK2.