Polo-like kinases mediate cell survival in mitochondrial dysfunction Export

@article{citeulike:5428400, abstract = {10.1073/pnas.0904229106 Cancer cells often display defects in mitochondrial respiration, thus the identification of pathways that promote cell survival under this metabolic state may have therapeutic implications. Here, we report that the targeted ablation of mitochondrial respiration markedly increases expression of Polo-like kinase 2 (PLK2) and that it is required for the in vitro growth of these nonrespiring cells. Furthermore, we identify PLK2 as a kinase that phosphorylates Ser-137 of PLK1, which is sufficient to mediate this survival signal. In vivo, knockdown of PLK2 in an isogenic human cell line with a modest defect in mitochondrial respiration eliminates xenograft formation, indicating that PLK2 activity is necessary for growth of cells with compromised respiration. Our findings delineate a mitochondrial dysfunction responsive cell cycle pathway critical for determining cancer cell outcome.}, author = {Matsumoto, Takumi and Wang, Ping-Yuan and Ma, Wenzhe and Sung, Ho J. and Matoba, Satoaki and Hwang, Paul M.}, citeulike-article-id = {5428400}, citeulike-linkout-0 = {http://dx.doi.org/10.1073/pnas.0904229106}, citeulike-linkout-1 = {http://www.pnas.org/content/early/2009/08/11/0904229106.abstract}, citeulike-linkout-2 = {http://www.pnas.org/content/early/2009/08/11/0904229106.full.pdf}, day = {11}, doi = {10.1073/pnas.0904229106}, journal = {Proceedings of the National Academy of Sciences}, keywords = {cell, cycle, mitochondria, plk1, plk2, respiration}, month = {August}, posted-at = {2009-08-12 19:08:00}, priority = {2}, title = {Polo-like kinases mediate cell survival in mitochondrial dysfunction}, url = {http://dx.doi.org/10.1073/pnas.0904229106}, year = {2009} }

TY - JOUR ID - citeulike:5428400 L3 - citeulike-article-id:5428400 N2 - 10.1073/pnas.0904229106 Cancer cells often display defects in mitochondrial respiration, thus the identification of pathways that promote cell survival under this metabolic state may have therapeutic implications. Here, we report that the targeted ablation of mitochondrial respiration markedly increases expression of Polo-like kinase 2 (PLK2) and that it is required for the in vitro growth of these nonrespiring cells. Furthermore, we identify PLK2 as a kinase that phosphorylates Ser-137 of PLK1, which is sufficient to mediate this survival signal. In vivo, knockdown of PLK2 in an isogenic human cell line with a modest defect in mitochondrial respiration eliminates xenograft formation, indicating that PLK2 activity is necessary for growth of cells with compromised respiration. Our findings delineate a mitochondrial dysfunction responsive cell cycle pathway critical for determining cancer cell outcome. JF - Proceedings of the National Academy of Sciences TI - Polo-like kinases mediate cell survival in mitochondrial dysfunction KW - cell KW - cycle KW - mitochondria KW - plk1 KW - plk2 KW - respiration AU - Matsumoto, Takumi AU - Wang, Ping-Yuan AU - Ma, Wenzhe AU - Sung, Ho AU - Matoba, Satoaki AU - Hwang, Paul PY - 2009/08/11/ UR - http://dx.doi.org/10.1073/pnas.0904229106 ER -