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      Potassium channels in cell cycle and cell proliferation

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          Abstract

          Normal cell-cycle progression is a crucial task for every multicellular organism, as it determines body size and shape, tissue renewal and senescence, and is also crucial for reproduction. On the other hand, dysregulation of the cell-cycle progression leading to uncontrolled cell proliferation is the hallmark of cancer. Therefore, it is not surprising that it is a tightly regulated process, with multifaceted and very complex control mechanisms. It is now well established that one of those mechanisms relies on ion channels, and in many cases specifically on potassium channels. Here, we summarize the possible mechanisms underlying the importance of potassium channels in cell-cycle control and briefly review some of the identified channels that illustrate the multiple ways in which this group of proteins can influence cell proliferation and modulate cell-cycle progression.

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          Most cited references106

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          Checkpoints: controls that ensure the order of cell cycle events.

          The events of the cell cycle of most organisms are ordered into dependent pathways in which the initiation of late events is dependent on the completion of early events. In eukaryotes, for example, mitosis is dependent on the completion of DNA synthesis. Some dependencies can be relieved by mutation (mitosis may then occur before completion of DNA synthesis), suggesting that the dependency is due to a control mechanism and not an intrinsic feature of the events themselves. Control mechanisms enforcing dependency in the cell cycle are here called checkpoints. Elimination of checkpoints may result in cell death, infidelity in the distribution of chromosomes or other organelles, or increased susceptibility to environmental perturbations such as DNA damaging agents. It appears that some checkpoints are eliminated during the early embryonic development of some organisms; this fact may pose special problems for the fidelity of embryonic cell division.
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            Genetic control of the cell division cycle in yeast.

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              Oncogenic potential of EAG K(+) channels.

              We have investigated the possible implication of the cell cycle-regulated K(+) channel ether à go-go (EAG) in cell proliferation and transformation. We show that transfection of EAG into mammalian cells confers a transformed phenotype. In addition, human EAG mRNA is detected in several somatic cancer cell lines, despite being preferentially expressed in brain among normal tissues. Inhibition of EAG expression in several of these cancer cell lines causes a significant reduction of cell proliferation. Moreover, the expression of EAG favours tumour progression when transfected cells are injected into immune-depressed mice. These data provide evidence for the oncogenic potential of EAG.
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                Author and article information

                Journal
                Philos Trans R Soc Lond B Biol Sci
                Philos. Trans. R. Soc. Lond., B, Biol. Sci
                RSTB
                royptb
                Philosophical Transactions of the Royal Society B: Biological Sciences
                The Royal Society
                0962-8436
                1471-2970
                19 March 2014
                19 March 2014
                : 369
                : 1638 , Theme Issue ‘Ion channels, transporters and cancer’ compiled and edited by Mustafa B. A. Djamgoz, R. Charles Coombes and Albrecht Schwab
                : 20130094
                Affiliations
                [1 ]Oncophysiology Group, Max Planck Institute of Experimental Medicine , Hermann-Rein-Strasse 3, Göttingen 37075, Germany
                [2 ]Department of Molecular Biology of Neuronal Signals, Max Planck Institute of Experimental Medicine , Hermann-Rein-Strasse 3, Göttingen 37075, Germany
                [3 ]Cluster of Excellence Nanoscale Microscopy and Molecular Physiology of the Brain , Göttingen, Germany
                Author notes

                One contribution of 17 to a Theme Issue ‘ Ion channels, transporters and cancer’.

                Article
                rstb20130094
                10.1098/rstb.2013.0094
                3917348
                24493742
                a143324c-316d-482e-8fe8-8ce71037c5d2

                © 2014 The Authors. Published by the Royal Society under the terms of the Creative Commons Attribution License http://creativecommons.org/licenses/by/3.0/, which permits unrestricted use, provided the original author and source are credited.

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                Custom metadata
                March 19, 2014

                Philosophy of science
                potassium channels,proliferation,cell cycle,cell division,cancer
                Philosophy of science
                potassium channels, proliferation, cell cycle, cell division, cancer

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