{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,15]],"date-time":"2026-04-15T19:28:39Z","timestamp":1776281319915,"version":"3.50.1"},"reference-count":51,"publisher":"Proceedings of the National Academy of Sciences","issue":"32","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2010,8,10]]},"abstract":"<jats:p>\n                    MAP kinase-interacting kinase 1 and 2 (Mnk1 and Mnk2) are protein-serine\/threonine kinases that are activated by ERK or p38 and phosphorylate eIF4E, which is involved in cap-dependent translation initiation. However, Mnk1\/2 double knockout (Mnk-DKO) mice show normal cell growth and development despite an absence of eIF4E phosphorylation. Here we show that the tumorigenesis occurring in the Lck-Pten mouse model (referred to here as tPten\n                    <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    mice) can be suppressed by the loss of Mnk1\/2. Phosphorylation of eIF4E was greatly enhanced in lymphomas of parental tPten\n                    <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    mice compared with lymphoid tissues of wild-type mice, but was totally absent in lymphomas of tPten\n                    <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    ; Mnk-DKO mice. Notably, stable knockdown of Mnk1 in the human glioma cell line U87MG resulted in dramatically decreased tumor formation when these cells were injected into athymic\n                    <jats:italic>nude<\/jats:italic>\n                    mice. Our data demonstrate an oncogenic role for Mnk1\/2 in tumor development, and highlight these molecules as potential anticancer drug targets that could be inactivated with minimal side effects.\n                  <\/jats:p>","DOI":"10.1073\/pnas.1008136107","type":"journal-article","created":{"date-parts":[[2010,8,2]],"date-time":"2010-08-02T23:35:49Z","timestamp":1280792149000},"page":"13984-13990","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":179,"title":["Combined deficiency for MAP kinase-interacting kinase 1 and 2 (Mnk1 and Mnk2) delays tumor development"],"prefix":"10.1073","volume":"107","author":[{"given":"Takeshi","family":"Ueda","sequence":"first","affiliation":[{"name":"The Campbell Family Institute for Breast Cancer Research, Ontario Cancer Institute, University Health Network, Toronto, ON, Canada M5G 2C1;"}]},{"given":"Masato","family":"Sasaki","sequence":"additional","affiliation":[{"name":"The Campbell Family Institute for Breast Cancer Research, Ontario Cancer Institute, University Health Network, Toronto, ON, Canada M5G 2C1;"}]},{"given":"Andrew J.","family":"Elia","sequence":"additional","affiliation":[{"name":"The Campbell Family Institute for Breast Cancer Research, Ontario Cancer Institute, University Health Network, Toronto, ON, Canada M5G 2C1;"}]},{"given":"Iok In Christine","family":"Chio","sequence":"additional","affiliation":[{"name":"The Campbell Family Institute for Breast Cancer Research, Ontario Cancer Institute, University Health Network, Toronto, ON, Canada M5G 2C1;"},{"name":"Department of Medical Biophysics, University of Toronto, Toronto, ON, Canada M5G 2C1;"}]},{"given":"Koichi","family":"Hamada","sequence":"additional","affiliation":[{"name":"Center for AIDS Research, Kumamoto University, 2-2-1 Honjo, Kumamoto 860-0811, Japan; and"}]},{"given":"Rikiro","family":"Fukunaga","sequence":"additional","affiliation":[{"name":"Department of Medical Chemistry, Graduate School of Medicine, Kyoto University, Yoshida-Konoe, Sakyo-ku, Kyoto 606-8501, Japan"}]},{"given":"Tak W.","family":"Mak","sequence":"additional","affiliation":[{"name":"The Campbell Family Institute for Breast Cancer Research, Ontario Cancer Institute, University Health Network, Toronto, ON, Canada M5G 2C1;"},{"name":"Department of Medical Biophysics, University of Toronto, Toronto, ON, Canada M5G 2C1;"}]}],"member":"341","published-online":{"date-parts":[[2010,8,2]]},"reference":[{"key":"e_1_3_3_1_2","doi-asserted-by":"publisher","DOI":"10.1093\/emboj\/16.8.1921"},{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1093\/emboj\/16.8.1909"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.19.3.1871"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1093\/emboj\/18.1.270"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0006-2952(00)00429-9"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.biochem.68.1.913"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.24.15.6539-6549.2004"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1038\/sj.onc.1207549"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature02369"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrc1819"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-08-3472"},{"key":"e_1_3_3_12_2","doi-asserted-by":"publisher","DOI":"10.1038\/nm1042"},{"key":"e_1_3_3_13_2","doi-asserted-by":"publisher","DOI":"10.4161\/cbt.8.15.8960"},{"key":"e_1_3_3_14_2","doi-asserted-by":"publisher","DOI":"10.1101\/gad.1604407"},{"key":"e_1_3_3_15_2","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-09-0986"},{"key":"e_1_3_3_16_2","first-page":"3940","article-title":"Gene expression profiling in polycythemia vera using cDNA microarray technology","volume":"63","author":"Pellagatti A","year":"2003","unstructured":"A Pellagatti, et al., Gene expression profiling in polycythemia vera using cDNA microarray technology. 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