Mitochondrial STAT3 Supports Ras-Dependent Oncogenic Transformation Export

@article{citeulike:5136063, abstract = {Signal transducer and activator of transcription 3 (STAT3) is a latent cytoplasmic transcription factor responsive to cytokine signaling and tyrosine kinase oncoproteins by nuclear translocation when it is tyrosine-phosphorylated. We report that malignant transformation by activated Ras is impaired without STAT3, in spite of the inability of Ras to drive STAT3 tyrosine phosphorylation or nuclear translocation. Moreover, STAT3 mutants that cannot be tyrosine-phosphorylated, that are retained in the cytoplasm, or that cannot bind DNA nonetheless supported Ras-mediated transformation. Unexpectedly, STAT3 was detected within mitochondria, and exclusive targeting of STAT3 to mitochondria without nuclear accumulation facilitated Ras transformation. Mitochondrial STAT3 sustained altered glycolytic and oxidative phosphorylation activities characteristic of cancer cells. Thus, in addition to its nuclear transcriptional role, STAT3 regulates a metabolic function in mitochondria, supporting Ras-dependent malignant transformation. 10.1126/science.1171721}, author = {Gough, Daniel J. and Corlett, Alicia and Schlessinger, Karni and Wegrzyn, Joanna and Larner, Andrew C. and Levy, David E.}, citeulike-article-id = {5136063}, citeulike-linkout-0 = {http://dx.doi.org/10.1126/science.1171721}, citeulike-linkout-1 = {http://www.sciencemag.org/cgi/content/abstract/324/5935/1713}, citeulike-linkout-2 = {http://view.ncbi.nlm.nih.gov/pubmed/19556508}, citeulike-linkout-3 = {http://www.hubmed.org/display.cgi?uids=19556508}, day = {26}, doi = {10.1126/science.1171721}, journal = {Science}, keywords = {arl, bart, ras, stat3}, month = {June}, number = {5935}, pages = {1713--1716}, posted-at = {2009-07-13 13:28:19}, priority = {2}, title = {Mitochondrial STAT3 Supports Ras-Dependent Oncogenic Transformation}, url = {http://dx.doi.org/10.1126/science.1171721}, volume = {324}, year = {2009} }

TY - JOUR ID - citeulike:5136063 L3 - citeulike-article-id:5136063 N2 - Signal transducer and activator of transcription 3 (STAT3) is a latent cytoplasmic transcription factor responsive to cytokine signaling and tyrosine kinase oncoproteins by nuclear translocation when it is tyrosine-phosphorylated. We report that malignant transformation by activated Ras is impaired without STAT3, in spite of the inability of Ras to drive STAT3 tyrosine phosphorylation or nuclear translocation. Moreover, STAT3 mutants that cannot be tyrosine-phosphorylated, that are retained in the cytoplasm, or that cannot bind DNA nonetheless supported Ras-mediated transformation. Unexpectedly, STAT3 was detected within mitochondria, and exclusive targeting of STAT3 to mitochondria without nuclear accumulation facilitated Ras transformation. Mitochondrial STAT3 sustained altered glycolytic and oxidative phosphorylation activities characteristic of cancer cells. Thus, in addition to its nuclear transcriptional role, STAT3 regulates a metabolic function in mitochondria, supporting Ras-dependent malignant transformation. 10.1126/science.1171721 IS - 5935 JF - Science EP - 1716 TI - Mitochondrial STAT3 Supports Ras-Dependent Oncogenic Transformation VL - 324 SP - 1713 KW - arl KW - bart KW - ras KW - stat3 AU - Gough, Daniel AU - Corlett, Alicia AU - Schlessinger, Karni AU - Wegrzyn, Joanna AU - Larner, Andrew AU - Levy, David PY - 2009/06/26/ UR - http://dx.doi.org/10.1126/science.1171721 ER -