Description
Low levels of the cell cycle regulator p27Kip1 are associated with a worse outcome in many tumor types. We report here a new regulatory role of p27Kip1 as a transcriptional regulator. In association with transcriptional repressors such as p130, E2F4 and HDACs, p27 binds to promoters of multiple genes leading to their repression. The p27Kip1-target genes participate in RNA processing, translation, respiration and cell cycle. Remarkably, p27Kip1-target genes are over-expressed in different human tumors in tight association with a poor clinical prognosis. We also observed a clear correlation between low levels of p27Kip1 and over-expression of p27Kip1-target genes in tumors. Overall, our findings indicate new tumor suppressor roles of p27Kip1 as a transcriptional regulator of genes relevant for oncogenesis.