A CDK-independent function of p27kip1 in the control of cell proliferation. Mus musculus

The integrated regulation of different intracellular signaling pathways is fundamental to ensure appropriate timing of cell division and, more in general, proper development of any living organism. Adopted mechanisms include the instauration of feedback regulations and/or to rely on a single molecule for the control of multiple processes. We now present evidences that in mammalian cells the CDK inhibitor p27kip1, by a CDK-independent and stathmin-dependent mechanism, is implicated in the control of the MAPK pathway, eventually influencing cell proliferation in vitro and mice growth in vivo. This p27kip1 activity regulates H-Ras driven transformation in mice and controls tumor progression in humans. Altogether, our work unveils a new mechanism that in mammalian cells contributes to proper regulation of cell proliferation and whose alteration may contribute to tumor onset and/or progression. Overall design: Four-condition experiment, 4 biological replicates of p27 Knock-out mices, 4 biological replicates of stathmin knock-out mices, 3 biological replicates of double knock-out (p27 & stathmin) mice3, 4 biological replicates of wild type mices. Reference design;