{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2024,8,6]],"date-time":"2024-08-06T02:03:01Z","timestamp":1722909781152},"reference-count":32,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2017,2,28]],"date-time":"2017-02-28T00:00:00Z","timestamp":1488240000000},"content-version":"vor","delay-in-days":27,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["25461404","26890001"],"award-info":[{"award-number":["25461404","26890001"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancer Science"],"published-print":{"date-parts":[[2017,2]]},"abstract":"Fusion tyrosine kinases play a crucial role in the development of hematological malignancies. FIP<\/jats:styled-content>1L1\u2010PDGFRA<\/jats:styled-content> is a leukemogenic fusion kinase that causes chronic eosinophilic leukemia. As a constitutively active kinase, FIP<\/jats:styled-content>1L1\u2010PDGFRA<\/jats:styled-content> stimulates downstream signaling molecules, leading to cellular proliferation and the generation of an anti\u2010apoptotic state. Contribution of the N\u2010terminal FIP<\/jats:styled-content>1L1 portion is necessary for FIP<\/jats:styled-content>1L1\u2010PDGFRA<\/jats:styled-content> to exert its full transforming activity, but the underlying mechanisms have not been fully characterized. We identified PIAS<\/jats:styled-content>1 as a FIP<\/jats:styled-content>1L1\u2010PDGFRA<\/jats:styled-content> association molecule by yeast two\u2010hybrid screening. Our analyses indicate that the FIP<\/jats:styled-content>1L1 portion of FIP<\/jats:styled-content>1L1\u2010PDGFRA<\/jats:styled-content> is required for efficient association with PIAS<\/jats:styled-content>1. As a consequence of the association, FIP<\/jats:styled-content>1L1\u2010PDGFRA<\/jats:styled-content> phosphorylates PIAS<\/jats:styled-content>1. Moreover, the kinase activity of FIP<\/jats:styled-content>1L1\u2010PDGFRA<\/jats:styled-content> stabilizes PIAS<\/jats:styled-content>1. Therefore, PIAS<\/jats:styled-content>1 is one of the downstream targets of FIP<\/jats:styled-content>1L1\u2010PDGFRA<\/jats:styled-content>. Moreover, we found that PIAS<\/jats:styled-content>1, as a SUMO<\/jats:styled-content> E3 ligase, sumoylates and stabilizes FIP<\/jats:styled-content>1L1\u2010PDGFRA<\/jats:styled-content>. In addition, suppression of PIAS<\/jats:styled-content>1 activity by a knockdown experiment resulted in destabilization of FIP<\/jats:styled-content>1L1\u2010PDGFRA<\/jats:styled-content>. Therefore, FIP<\/jats:styled-content>1L1\u2010PDGFRA<\/jats:styled-content> and PIAS<\/jats:styled-content>1 form a positive cross\u2010talk through their enzymatic activities. Suppression of sumoylation by ginkgolic acid, a small molecule compound inhibiting a SUMO<\/jats:styled-content> E1\u2010activating enzyme, also destabilizes FIP<\/jats:styled-content>1L1\u2010PDGFRA<\/jats:styled-content>, and while the tyrosine kinase inhibitor imatinib suppresses FIP<\/jats:styled-content>1L1\u2010PDGFRA<\/jats:styled-content>\u2010dependent cell growth, ginkgolic acid or siRNA<\/jats:styled-content> of PIAS<\/jats:styled-content>1 has a synergistic effect with imatinib. In conclusion, our results suggest that sumoylation by PIAS<\/jats:styled-content>1 is a potential target in the treatment of FIP<\/jats:styled-content>1L1\u2010PDGFRA<\/jats:styled-content>\u2010positive chronic eosinophilic leukemia.<\/jats:p>","DOI":"10.1111\/cas.13129","type":"journal-article","created":{"date-parts":[[2016,12,13]],"date-time":"2016-12-13T20:46:44Z","timestamp":1481662004000},"page":"200-207","source":"Crossref","is-referenced-by-count":3,"title":["Leukemogenic kinase FIP<\/scp>1L1\u2010PDGFRA<\/scp> and a small ubiquitin\u2010like modifier E3 ligase, PIAS<\/scp>1, form a positive cross\u2010talk through their enzymatic activities"],"prefix":"10.1111","volume":"108","author":[{"given":"Makoto","family":"Ibata","sequence":"first","affiliation":[{"name":"Department of Hematology Hokkaido University Graduate School of Medicine Sapporo Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Junko","family":"Iwasaki","sequence":"additional","affiliation":[{"name":"Department of Hematology Hokkaido University Graduate School of Medicine Sapporo Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yoichiro","family":"Fujioka","sequence":"additional","affiliation":[{"name":"Department of Cell Physiology Hokkaido University Graduate School of Medicine Sapporo Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Koji","family":"Nakagawa","sequence":"additional","affiliation":[{"name":"Department of Laboratory of Pathophysiology and Therapeutics Hokkaido University Faculty of Pharmaceutical Sciences Sapporo Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Stephanie","family":"Darmanin","sequence":"additional","affiliation":[{"name":"Department of Center for Hematology and Regenerative Medicine Department of Medicine Karolinska University Hospital Huddinge Sweden"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Masahiro","family":"Onozawa","sequence":"additional","affiliation":[{"name":"Department of Hematology Hokkaido University Graduate School of Medicine Sapporo Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Daigo","family":"Hashimoto","sequence":"additional","affiliation":[{"name":"Department of Hematology Hokkaido University Graduate School of Medicine Sapporo Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yusuke","family":"Ohba","sequence":"additional","affiliation":[{"name":"Department of Cell Physiology Hokkaido University Graduate School of Medicine Sapporo Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shigetsugu","family":"Hatakeyama","sequence":"additional","affiliation":[{"name":"Department of Biochemistry Hokkaido University Graduate School of Medicine Sapporo Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Takanori","family":"Teshima","sequence":"additional","affiliation":[{"name":"Department of Hematology Hokkaido University Graduate School of Medicine Sapporo Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Takeshi","family":"Kondo","sequence":"additional","affiliation":[{"name":"Department of Hematology Hokkaido University Graduate School of Medicine Sapporo Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2017,2,28]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/B978-0-12-386041-5.00004-2"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1042\/BJ20100158"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.95.18.10626"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/nri1667"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.01592-13"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa025217"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0932698100"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2004-03-0787"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.leu.2403722"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00277-007-0357-8"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2006-10-050054"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.3324\/haematol.11420"},{"key":"e_1_2_7_14_1","volume-title":"World Health Organization Classification of Tumours of Haematopoietic and Lymphoid Tissue","author":"Swerdlow SH","year":"2008"},{"key":"e_1_2_7_15_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0601192103"},{"key":"e_1_2_7_16_1","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-06-4183"},{"key":"e_1_2_7_17_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00277-014-2085-1"},{"key":"e_1_2_7_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbrc.2007.12.063"},{"key":"e_1_2_7_19_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M807489200"},{"key":"e_1_2_7_20_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0034912"},{"key":"e_1_2_7_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.molonc.2014.02.003"},{"key":"e_1_2_7_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0014-5793(03)01268-7"},{"key":"e_1_2_7_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0014-5793(02)03486-5"},{"key":"e_1_2_7_24_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M314023200"},{"key":"e_1_2_7_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.chembiol.2009.01.009"},{"key":"e_1_2_7_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.exphem.2011.02.001"},{"key":"e_1_2_7_27_1","doi-asserted-by":"publisher","DOI":"10.3324\/haematol.2008.001149"},{"key":"e_1_2_7_28_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2007.03.056"},{"key":"e_1_2_7_29_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.molcel.2009.01.013"},{"key":"e_1_2_7_30_1","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-13-0538"},{"key":"e_1_2_7_31_1","doi-asserted-by":"publisher","DOI":"10.1038\/leu.2008.309"},{"key":"e_1_2_7_32_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2007-07-100164"},{"key":"e_1_2_7_33_1","doi-asserted-by":"publisher","DOI":"10.1002\/embj.201283326"}],"container-title":["Cancer Science"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Fcas.13129","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/cas.13129","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,3]],"date-time":"2023-10-03T01:39:45Z","timestamp":1696297185000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/cas.13129"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2017,2]]},"references-count":32,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2017,2]]}},"alternative-id":["10.1111\/cas.13129"],"URL":"https:\/\/doi.org\/10.1111\/cas.13129","archive":["Portico"],"relation":{},"ISSN":["1347-9032","1349-7006"],"issn-type":[{"value":"1347-9032","type":"print"},{"value":"1349-7006","type":"electronic"}],"subject":[],"published":{"date-parts":[[2017,2]]}}}