Morishita D et al. - Pim-mediated phosphorylation and inactivation of forkhead transcription factors, FoxO1a and FoxO3a, was involved in the transcriptional repression of the p27Kip1 gene. In contrast, inhibition of Pim signaling by expressing the dominant-negative form of Pim1 increased nuclear p27Kip1 level and attenuated cell proliferation. Because the CDK inhibitor p27Kip1 plays a crucial role in tumor suppression by inhibiting abnormal cell cycle progression, Pim kinases promote cell cycle progression and tumorigenesis by down-regulating p27Kip1 expression at both transcriptional and posttranslational levels.
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