{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2024,6,22]],"date-time":"2024-06-22T06:46:08Z","timestamp":1719038768451},"reference-count":51,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2011,2,22]],"date-time":"2011-02-22T00:00:00Z","timestamp":1298332800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Journal Cellular Physiology"],"published-print":{"date-parts":[[2011,5]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Metabolites and derivatives of vitamin D are well\u2010known inducers of monocytic differentiation, but the mechanistic basis for their action is not fully elucidated. Here we show that the product of protooncogene Cot1 represses the monocytic phenotype in human acute myeloid leukemia (AML) cells induced to differentiate by 1,25\u2010dihydroxyvitamin D<jats:sub>3<\/jats:sub> (1,25D), even though the expression of cellular Cot1 increases early in the process of 1,25D\u2010induced differentiation. Interestingly, the expression of the two members of the Kinase Suppressor of Ras (KSR) family of molecular scaffolds, known to be positive regulators of Ras signaling and of 1,25D\u2010induced differentiation, increases in parallel with Cot1 in 1,25D\u2010treated cells. However, KSR1\/2 are negatively regulated by Cot1, as determined by transfection of siCot1, and confirmed by a reverse effect of ectopic expression of Cot1. The effect of Cot1 in AML cells appears to be cell\u2010type specific, as previous reports in other cell types found KSR\u20102 to be a negative regulator of Cot1, a reverse relationship. Also in contrast to findings in other cells, in AML cells Cot1 exerts negative control on the MAP kinase pathways, since siCot1 increases the levels of activated Raf1, p90RSK, JNK1, c\u2010jun, and p38, though not of MEK\/ERK. These findings have implications for therapy of AML, since in AML cells active MAPKs hasten cell differentiation, and specific pharmacological inhibitors of Cot1 kinase activity have recently became available, thus making Cot1 a \u201cdruggable\u201d target. J. Cell. Physiol. 226: 1232\u20131240, 2011. \u00a9 2010 Wiley\u2010Liss, Inc.<\/jats:p>","DOI":"10.1002\/jcp.22449","type":"journal-article","created":{"date-parts":[[2010,10,13]],"date-time":"2010-10-13T14:19:38Z","timestamp":1286979578000},"page":"1232-1240","source":"Crossref","is-referenced-by-count":5,"title":["Oncoprotein Cot1 represses kinase suppressors of Ras1\/2 and 1,25\u2010dihydroxyvitamin D<sub>3<\/sub>\u2010induced differentiation of human acute myeloid leukemia cells"],"prefix":"10.1002","volume":"226","author":[{"given":"Xuening","family":"Wang","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"George P.","family":"Studzinski","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2011,2,22]]},"reference":[{"key":"e_1_2_6_2_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.78.8.4990"},{"key":"e_1_2_6_3_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcp.22240"},{"key":"e_1_2_6_4_1","doi-asserted-by":"publisher","DOI":"10.1002\/1097-0142(20010615)91:12<2431::AID-CNCR1278>3.0.CO;2-3"},{"key":"e_1_2_6_5_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M306002200"},{"key":"e_1_2_6_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbrc.2005.07.009"},{"key":"e_1_2_6_7_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V78.10.2696.2696"},{"key":"e_1_2_6_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.leukres.2009.03.003"},{"key":"e_1_2_6_9_1","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.20.5.1747-1758.2000"},{"key":"e_1_2_6_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.yexcr.2004.04.029"},{"key":"e_1_2_6_11_1","doi-asserted-by":"publisher","DOI":"10.1093\/jnci\/93.16.1224"},{"key":"e_1_2_6_12_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M412837200"},{"key":"e_1_2_6_13_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.onc.1204763"},{"key":"e_1_2_6_14_1","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.15.8.4125"},{"key":"e_1_2_6_15_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V54.3.713.713"},{"key":"e_1_2_6_16_1","first-page":"295","article-title":"Mycoplasma detection in cell cultures: A comparison of four methods","volume":"57","author":"Garner CM","year":"2000","journal-title":"Br J Biomed Sci"},{"key":"e_1_2_6_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bmcl.2005.08.029"},{"key":"e_1_2_6_18_1","doi-asserted-by":"publisher","DOI":"10.1080\/10408360902982128"},{"key":"e_1_2_6_19_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.onc.1202431"},{"key":"e_1_2_6_20_1","doi-asserted-by":"publisher","DOI":"10.1248\/bpb.33.133"},{"key":"e_1_2_6_21_1","doi-asserted-by":"publisher","DOI":"10.4161\/cc.7.7.5620"},{"key":"e_1_2_6_22_1","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-03-3029"},{"key":"e_1_2_6_23_1","first-page":"1399","article-title":"1,25\u2010Dihydroxyvitamin D3: In vivo and in vitro effects on human preleukemic and leukemic cells","volume":"69","author":"Koeffler HP","year":"1985","journal-title":"Cancer Treat Rep"},{"key":"e_1_2_6_24_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrm1743"},{"key":"e_1_2_6_25_1","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2009.813"},{"key":"e_1_2_6_26_1","first-page":"101","article-title":"Control of the ERK MAP kinase cascade by Ras and Raf","volume":"27","author":"Marais R","year":"1996","journal-title":"Cancer Surv"},{"key":"e_1_2_6_27_1","doi-asserted-by":"publisher","DOI":"10.1006\/bbrc.1997.7832"},{"key":"e_1_2_6_28_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.yexcr.2006.03.003"},{"key":"e_1_2_6_29_1","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.11.8.4088"},{"key":"e_1_2_6_30_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0145-2126(96)00089-6"},{"key":"e_1_2_6_31_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI112593"},{"key":"e_1_2_6_32_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.90.6.2251"},{"key":"e_1_2_6_33_1","doi-asserted-by":"publisher","DOI":"10.1002\/j.1460-2075.1996.tb00417.x"},{"key":"e_1_2_6_34_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.leu.2403528"},{"key":"e_1_2_6_35_1","doi-asserted-by":"publisher","DOI":"10.1159\/000163849"},{"key":"e_1_2_6_36_1","doi-asserted-by":"publisher","DOI":"10.1002\/ijc.21736"},{"key":"e_1_2_6_37_1","doi-asserted-by":"publisher","DOI":"10.3181\/00379727-179-42098"},{"key":"e_1_2_6_38_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jsbmb.2005.06.010"},{"key":"e_1_2_6_39_1","doi-asserted-by":"publisher","DOI":"10.1002\/ijc.2910170504"},{"key":"e_1_2_6_40_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V99.3.759"},{"key":"e_1_2_6_41_1","doi-asserted-by":"publisher","DOI":"10.1042\/bj2040713"},{"key":"e_1_2_6_42_1","doi-asserted-by":"publisher","DOI":"10.1002\/1097-4644(20010315)80:4<471::AID-JCB1001>3.0.CO;2-J"},{"key":"e_1_2_6_43_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcp.10443"},{"key":"e_1_2_6_44_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcp.20731"},{"key":"e_1_2_6_45_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jsbmb.2010.03.016"},{"key":"e_1_2_6_46_1","doi-asserted-by":"publisher","DOI":"10.1093\/jnci\/89.16.1199"},{"key":"e_1_2_6_47_1","doi-asserted-by":"publisher","DOI":"10.1006\/excr.2000.4939"},{"key":"e_1_2_6_48_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcb.10595"},{"key":"e_1_2_6_49_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.onc.1209697"},{"key":"e_1_2_6_50_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.yexcr.2007.05.021"},{"key":"e_1_2_6_51_1","doi-asserted-by":"publisher","DOI":"10.1002\/hon.929"},{"key":"e_1_2_6_52_1","article-title":"Isoforms of p38MAPK gamma and delta contribute to differentiation of human AML cells induced by 1,25\u2010dihydroxyvitamin D3","author":"Zhang J","year":"2010","journal-title":"Exp Cell Res"}],"container-title":["Journal of Cellular Physiology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fjcp.22449","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/jcp.22449","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,16]],"date-time":"2023-10-16T20:49:17Z","timestamp":1697489357000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/jcp.22449"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2011,2,22]]},"references-count":51,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2011,5]]}},"alternative-id":["10.1002\/jcp.22449"],"URL":"https:\/\/doi.org\/10.1002\/jcp.22449","archive":["Portico"],"relation":{},"ISSN":["0021-9541","1097-4652"],"issn-type":[{"value":"0021-9541","type":"print"},{"value":"1097-4652","type":"electronic"}],"subject":[],"published":{"date-parts":[[2011,2,22]]}}}