title: Meet me in the cytoplasm: A role for p27(Kip1) in the control of H-Ras.
abstract: The small GTPases of the Ras family play a pivotal role in the regulation of cell proliferation and motility, both in normal and transformed cells. In particular, the 3 genes encoding for the N-, H- and K-Ras are frequently mutated in human cancer and their inappropriate regulation, expression and subcellular localization can drive tumor onset and progression. Activation of the Ras-MAPK pathway directly signals on the cell cycle machinery by regulating the expression and/or localization of 2 key cell cycle player, Cyclin D1 and p27(Kip1). We recently reported that in normal fibroblasts, following mitogenic stimuli, p27(Kip1) translocates to the cytoplasm where it regulates H-Ras localization and activity. This regulatory mechanism ensures that cells pass beyond the restriction point of the cell cycle only when the proper level of stimulation is reached. Here, we comment on this new evidence that possibly represents one of the ways that cells have developed during evolution to ensure that the cell decision to divide is taken only when time and context are appropriate.
authors.affiliation: a Division of Experimental Oncology 2, Department of Translational Research, C.R.O. Aviano IRCCS, National Cancer Institute , Aviano , Italy.
authors.forename: Gustavo
authors.initials: G
authors.lastname: Baldassarre
authors.affiliation: a Division of Experimental Oncology 2, Department of Translational Research, C.R.O. Aviano IRCCS, National Cancer Institute , Aviano , Italy.
authors.forename: Barbara
authors.initials: B
authors.lastname: Belletti
mesh_terms: D000818:Animals; D050760:Cyclin-Dependent Kinase Inhibitor p27 / Q000378:metabolism*; D003593:Cytoplasm / Q000378:metabolism*; D006801:Humans; D015398:Signal Transduction; D018631:ras Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: D050760:Cyclin-Dependent Kinase Inhibitor p27; D018631:ras Proteins
keywords: H-Ras; K-Ras; cell cycle; microtubule stability; motility; p27kip; proliferation; stathmin