Expression data from p27WT, p27CK and KO MEFs cells in quiescence

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 factors such as ETS and E2F4 and co-repressors like p130, HDACs and mSin3A, p27 binds to promoters of multiple genes leading to their repression. The p27-target genes participate in RNA processing, translation, respiration and cell cycle. Remarkably, p27-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 p27 and over-expression of p27-target genes in tumors. Overall, our findings indicate new tumor suppressor roles of p271 as a transcriptional regulator of genes relevant for oncogenesis.

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Pippa R, Espinosa L, Gundem G, García-Escudero R, Dominguez A, Orlando S, Gallastegui E, Saiz C, Besson A, Pujol MJ, López-Bigas N, Paramio JM, Bigas A, Bachs O