Transcriptional activation of Skp2 by BCR-ABL in K562 chronic myeloid leukemia cells.

We addressed how BCR-ABL oncoprotein increased Skp2 expression. Treatment of Imatinib or LY294002 reduced Skp2 mRNA in BCR-ABL-positive K562 cells. Knockdown of AKT by small hairpin RNA also reduced Skp2 expression. We found that BCR-ABL up-regulated Skp2 via Sp1 because (1) the Sp1 site located at the -386/-380 promoter region was important for BCR-ABL-induced Skp2 promoter activity, (2) chromatin immunoprecipitation assay demonstrated that Imatinib inhibited the recruitment of p300 to the Sp1 site of Skp2 promoter and (3) knockdown of Sp1 reduced Skp2 expression in K562 cells. These results suggest that BCR-ABL controls Skp2 gene transcription via the PI3K/AKT/Sp1 pathway.