{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,16]],"date-time":"2026-03-16T21:34:07Z","timestamp":1773696847095,"version":"3.50.1"},"reference-count":56,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2016,6,22]],"date-time":"2016-06-22T00:00:00Z","timestamp":1466553600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2016,6,22]],"date-time":"2016-06-22T00:00:00Z","timestamp":1466553600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Sci Rep"],"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Chronic myeloid leukemia (CML) is characterized by constitutively active fusion protein tyrosine kinase BCR-ABL. Although the tyrosine kinase inhibitor (TKI) against BCR-ABL, imatinib, is the first-line therapy for CML, acquired resistance almost inevitably emerges. The underlying mechanism are point mutations within the <jats:italic>BCR<\/jats:italic>-<jats:italic>ABL<\/jats:italic> gene, among which T315I is notorious because it resists to almost all currently available inhibitors. Here we took use of a previously generated chimeric ubiquitin ligase, SH2-U-box, in which SH2 from the adaptor protein Grb2 acts as a binding domain for activated BCR-ABL, while U-box from CHIP functions as an E3 ubiquitin ligase domain, so as to target the ubiquitination and degradation of both native and T315I-mutant BCR-ABL. As such, SH2-U-box significantly inhibited proliferation and induced apoptosis in CML cells harboring either the wild-type or T315I-mutant BCR-ABL (K562 or K562R), with BCR-ABL-dependent signaling pathways being repressed. Moreover, SH2-U-box worked in concert with imatinib in K562 cells. Importantly, SH2-U-box-carrying lentivirus could markedly suppress the growth of K562-xenografts in nude mice or K562R-xenografts in SCID mice, as well as that of primary CML cells. Collectively, by degrading the native and T315I-mutant BCR-ABL, the chimeric ubiquitin ligase SH2-U-box may serve as a potential therapy for both imatinib-sensitive and resistant CML.<\/jats:p>","DOI":"10.1038\/srep28352","type":"journal-article","created":{"date-parts":[[2016,6,23]],"date-time":"2016-06-23T05:35:36Z","timestamp":1466660136000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":22,"title":["The chimeric ubiquitin ligase SH2-U-box inhibits the growth of imatinib-sensitive and resistant CML by targeting the native and T315I-mutant BCR-ABL"],"prefix":"10.1038","volume":"6","author":[{"given":"Yi","family":"Ru","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Qinhao","family":"Wang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiping","family":"Liu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mei","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Daixing","family":"Zhong","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mingxiang","family":"Ye","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yuanchun","family":"Li","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hua","family":"Han","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Libo","family":"Yao","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xia","family":"Li","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2016,6,22]]},"reference":[{"key":"BFsrep28352_CR1","doi-asserted-by":"crossref","first-page":"220","DOI":"10.1179\/102453309X426245","volume":"14","author":"M Sonmez","year":"2009","unstructured":"Sonmez, M. et al. Effect of LMO2 protein expression on survival in chronic myeloid leukemia patients treated with imatinib mesylate. Hematology 14, 220\u2013223 (2009).","journal-title":"Hematology"},{"key":"BFsrep28352_CR2","doi-asserted-by":"crossref","first-page":"1432","DOI":"10.1038\/leu.2009.49","volume":"23","author":"R Naughton","year":"2009","unstructured":"Naughton, R., Quiney, C., Turner, S. D. & Cotter, T. G. Bcr-Abl-mediated redox regulation of the PI3K\/AKT pathway. Leukemia 23, 1432\u20131440 (2009).","journal-title":"Leukemia"},{"key":"BFsrep28352_CR3","doi-asserted-by":"crossref","first-page":"380","DOI":"10.1038\/nature15248","volume":"525","author":"S Prost","year":"2015","unstructured":"Prost, S. et al. Erosion of the chronic myeloid leukaemia stem cell pool by PPARgamma agonists. Nature 525, 380\u2013383 (2015).","journal-title":"Nature"},{"key":"BFsrep28352_CR4","doi-asserted-by":"crossref","first-page":"118","DOI":"10.1038\/leu.2012.222","volume":"27","author":"FU Wohrle","year":"2013","unstructured":"Wohrle, F. U. et al. Gab2 signaling in chronic myeloid leukemia cells confers resistance to multiple Bcr-Abl inhibitors. Leukemia 27, 118\u2013129 (2013).","journal-title":"Leukemia"},{"key":"BFsrep28352_CR5","doi-asserted-by":"crossref","first-page":"1666","DOI":"10.1038\/leu.2013.40","volume":"27","author":"LC Gillis","year":"2013","unstructured":"Gillis, L. C., Berry, D. M., Minden, M. D., McGlade, C. J. & Barber, D. L. Gads (Grb2-related adaptor downstream of Shc) is required for BCR-ABL-mediated lymphoid leukemia. Leukemia 27, 1666\u20131676 (2013).","journal-title":"Leukemia"},{"key":"BFsrep28352_CR6","doi-asserted-by":"crossref","first-page":"590","DOI":"10.1038\/nchembio.954","volume":"8","author":"W Jankowski","year":"2012","unstructured":"Jankowski, W. et al. Domain organization differences explain Bcr-Abl\u2019s preference for CrkL over CrkII. Nature chemical biology 8, 590\u2013596 (2012).","journal-title":"Nature chemical biology"},{"key":"BFsrep28352_CR7","doi-asserted-by":"crossref","first-page":"7325","DOI":"10.1158\/0008-5472.CAN-10-0607","volume":"70","author":"JH Seo","year":"2010","unstructured":"Seo, J. H. et al. A specific need for CRKL in p210BCR-ABL-induced transformation of mouse hematopoietic progenitors. Cancer research 70, 7325\u20137335 (2010).","journal-title":"Cancer research"},{"key":"BFsrep28352_CR8","doi-asserted-by":"crossref","unstructured":"Xishan, Z., Ziying, L., Jing, D. & Gang, L. MicroRNA-320a acts as a tumor suppressor by targeting BCR\/ABL oncogene in chronic myeloid leukemia. Scientific reports 5, 12460 (2015).","DOI":"10.1038\/srep12460"},{"key":"BFsrep28352_CR9","doi-asserted-by":"crossref","first-page":"390","DOI":"10.1182\/blood-2010-11-316760","volume":"118","author":"Y Chen","year":"2011","unstructured":"Chen, Y. et al. A tumor suppressor function of the Msr1 gene in leukemia stem cells of chronic myeloid leukemia. Blood 118, 390\u2013400 (2011).","journal-title":"Blood"},{"key":"BFsrep28352_CR10","doi-asserted-by":"crossref","first-page":"3723","DOI":"10.1182\/blood-2007-09-114454","volume":"111","author":"E Weisberg","year":"2008","unstructured":"Weisberg, E. et al. Potentiation of antileukemic therapies by the dual PI3K\/PDK-1 inhibitor, BAG956: effects on BCR-ABL- and mutant FLT3-expressing cells. Blood 111, 3723\u20133734 (2008).","journal-title":"Blood"},{"key":"BFsrep28352_CR11","doi-asserted-by":"crossref","first-page":"276","DOI":"10.1016\/j.molonc.2012.02.002","volume":"6","author":"S Nam","year":"2012","unstructured":"Nam, S. et al. Indirubin derivatives induce apoptosis of chronic myelogenous leukemia cells involving inhibition of Stat5 signaling. Molecular oncology 6, 276\u2013283 (2012).","journal-title":"Molecular oncology"},{"key":"BFsrep28352_CR12","doi-asserted-by":"crossref","first-page":"e7439","DOI":"10.1371\/journal.pone.0007439","volume":"4","author":"KJ Johnson","year":"2009","unstructured":"Johnson, K. J. et al. A BCR-ABL mutant lacking direct binding sites for the GRB2, CBL and CRKL adapter proteins fails to induce leukemia in mice. PloS one 4, e7439 (2009).","journal-title":"PloS one"},{"key":"BFsrep28352_CR13","doi-asserted-by":"crossref","first-page":"12974","DOI":"10.1038\/srep12974","volume":"5","author":"YH Huang","year":"2015","unstructured":"Huang, Y. H. et al. Design of substrate-based BCR-ABL kinase inhibitors using the cyclotide scaffold. Scientific reports 5, 12974 (2015).","journal-title":"Scientific reports"},{"key":"BFsrep28352_CR14","doi-asserted-by":"crossref","first-page":"1220","DOI":"10.1038\/sj.leu.2402565","volume":"16","author":"T Fischer","year":"2002","unstructured":"Fischer, T. et al. Safety and efficacy of STI-571 (imatinib mesylate) in patients with bcr\/abl-positive chronic myelogenous leukemia (CML) after autologous peripheral blood stem cell transplantation (PBSCT). Leukemia 16, 1220\u20131228 (2002).","journal-title":"Leukemia"},{"key":"BFsrep28352_CR15","doi-asserted-by":"crossref","first-page":"1213","DOI":"10.1038\/sj.leu.2402555","volume":"16","author":"P La Rosee","year":"2002","unstructured":"La Rosee, P., O\u2019Dwyer, M. E. & Druker, B. J. Insights from pre-clinical studies for new combination treatment regimens with the Bcr-Abl kinase inhibitor imatinib mesylate (Gleevec\/Glivec) in chronic myelogenous leukemia: a translational perspective. Leukemia 16, 1213\u20131219 (2002).","journal-title":"Leukemia"},{"key":"BFsrep28352_CR16","doi-asserted-by":"crossref","first-page":"S15","DOI":"10.1053\/j.seminhematol.2006.12.002","volume":"44","author":"A Hochhaus","year":"2007","unstructured":"Hochhaus, A., Erben, P., Ernst, T. & Mueller, M. C. Resistance to targeted therapy in chronic myelogenous leukemia. Seminars in hematology 44, S15\u201324 (2007).","journal-title":"Seminars in hematology"},{"key":"BFsrep28352_CR17","doi-asserted-by":"crossref","first-page":"901","DOI":"10.1182\/blood-2014-09-594432","volume":"125","author":"P Valent","year":"2015","unstructured":"Valent, P. et al. Vascular safety issues in CML patients treated with BCR\/ABL1 kinase inhibitors. Blood 125, 901\u2013906 (2015).","journal-title":"Blood"},{"key":"BFsrep28352_CR18","doi-asserted-by":"crossref","first-page":"1123","DOI":"10.1038\/leu.2015.36","volume":"29","author":"L Kalmanti","year":"2015","unstructured":"Kalmanti, L. et al. Safety and efficacy of imatinib in CML over a period of 10 years: data from the randomized CML-study IV. Leukemia 29, 1123\u20131132 (2015).","journal-title":"Leukemia"},{"key":"BFsrep28352_CR19","doi-asserted-by":"crossref","first-page":"2879","DOI":"10.1182\/blood-2015-03-632174","volume":"125","author":"M Muschen","year":"2015","unstructured":"Muschen, M. Ph+ ALL: drawing strength from a benign past. Blood 125, 2879\u20132880 (2015).","journal-title":"Blood"},{"key":"BFsrep28352_CR20","doi-asserted-by":"crossref","first-page":"1832","DOI":"10.1038\/leu.2015.168","volume":"29","author":"TP Hughes","year":"2015","unstructured":"Hughes, T. P. et al. BCR-ABL1 mutation development during first-line treatment with dasatinib or imatinib for chronic myeloid leukemia in chronic phase. Leukemia 29, 1832\u20131838 (2015).","journal-title":"Leukemia"},{"key":"BFsrep28352_CR21","doi-asserted-by":"crossref","first-page":"1510","DOI":"10.3324\/haematol.2012.080234","volume":"98","author":"FE Nicolini","year":"2013","unstructured":"Nicolini, F. E. et al. The BCR-ABLT315I mutation compromises survival in chronic phase chronic myelogenous leukemia patients resistant to tyrosine kinase inhibitors, in a matched pair analysis. Haematologica 98, 1510\u20131516 (2013).","journal-title":"Haematologica"},{"key":"BFsrep28352_CR22","doi-asserted-by":"crossref","first-page":"1061","DOI":"10.1038\/sj.leu.2404236","volume":"20","author":"FE Nicolini","year":"2006","unstructured":"Nicolini, F. E. et al. Mutation status and clinical outcome of 89 imatinib mesylate-resistant chronic myelogenous leukemia patients: a retrospective analysis from the French intergroup of CML (Fi(phi)-LMC GROUP). Leukemia 20, 1061\u20131066 (2006).","journal-title":"Leukemia"},{"key":"BFsrep28352_CR23","doi-asserted-by":"crossref","first-page":"1783","DOI":"10.1056\/NEJMoa1306494","volume":"369","author":"JE Cortes","year":"2013","unstructured":"Cortes, J. E. et al. A phase 2 trial of ponatinib in Philadelphia chromosome-positive leukemias. The New England journal of medicine 369, 1783\u20131796 (2013).","journal-title":"The New England journal of medicine"},{"key":"BFsrep28352_CR24","doi-asserted-by":"crossref","first-page":"2075","DOI":"10.1056\/NEJMoa1205127","volume":"367","author":"JE Cortes","year":"2012","unstructured":"Cortes, J. E. et al. Ponatinib in refractory Philadelphia chromosome-positive leukemias. The New England journal of medicine 367, 2075\u20132088 (2012).","journal-title":"The New England journal of medicine"},{"key":"BFsrep28352_CR25","doi-asserted-by":"crossref","first-page":"81","DOI":"10.1038\/373081a0","volume":"373","author":"M Scheffner","year":"1995","unstructured":"Scheffner, M., Nuber, U. & Huibregtse, J. M. Protein ubiquitination involving an E1-E2-E3 enzyme ubiquitin thioester cascade. Nature 373, 81\u201383 (1995).","journal-title":"Nature"},{"key":"BFsrep28352_CR26","doi-asserted-by":"crossref","first-page":"1393","DOI":"10.1038\/cdd.2011.16","volume":"18","author":"P de Bie","year":"2011","unstructured":"de Bie, P. & Ciechanover, A. Ubiquitination of E3 ligases: self-regulation of the ubiquitin system via proteolytic and non-proteolytic mechanisms. Cell death and differentiation 18, 1393\u20131402 (2011).","journal-title":"Cell death and differentiation"},{"key":"BFsrep28352_CR27","doi-asserted-by":"crossref","first-page":"2563","DOI":"10.1073\/pnas.92.7.2563","volume":"92","author":"JM Huibregtse","year":"1995","unstructured":"Huibregtse, J. M., Scheffner, M., Beaudenon, S. & Howley, P. M. A family of proteins structurally and functionally related to the E6-AP ubiquitin-protein ligase. Proc Natl Acad Sci USA 92, 2563\u20132567 (1995).","journal-title":"Proc Natl Acad Sci USA"},{"key":"BFsrep28352_CR28","doi-asserted-by":"crossref","first-page":"11364","DOI":"10.1073\/pnas.96.20.11364","volume":"96","author":"KL Lorick","year":"1999","unstructured":"Lorick, K. L. et al. RING fingers mediate ubiquitin-conjugating enzyme (E2)-dependent ubiquitination. Proc Natl Acad Sci USA 96, 11364\u201311369 (1999).","journal-title":"Proc Natl Acad Sci USA"},{"key":"BFsrep28352_CR29","doi-asserted-by":"crossref","first-page":"42938","DOI":"10.1074\/jbc.M101968200","volume":"276","author":"J Jiang","year":"2001","unstructured":"Jiang, J. et al. CHIP is a U-box-dependent E3 ubiquitin ligase: identification of Hsc70 as a target for ubiquitylation. J Biol Chem 276, 42938\u201342944 (2001).","journal-title":"J Biol Chem"},{"issue":"1","key":"BFsrep28352_CR30","doi-asserted-by":"crossref","first-page":"122","DOI":"10.1016\/j.bbamcr.2012.10.010","volume":"1833","author":"Bhopal Mohapatra","year":"2013","unstructured":"Mohapatra, B. et al. Protein tyrosine kinase regulation by ubiquitination: critical roles of Cbl-family ubiquitin ligases. Biochimica et biophysica acta 1833, 122\u2013139.","journal-title":"Biochimica et Biophysica Acta (BBA) - Molecular Cell Research"},{"key":"BFsrep28352_CR31","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1016\/j.biocel.2014.10.027","volume":"58","author":"I Paul","year":"2015","unstructured":"Paul, I. & Ghosh, M. K. A CHIPotle in physiology and disease. Int J Biochem Cell Biol 58, 37\u201352 (2015).","journal-title":"Int J Biochem Cell Biol"},{"key":"BFsrep28352_CR32","doi-asserted-by":"crossref","first-page":"8716","DOI":"10.1158\/0008-5472.CAN-06-3731","volume":"67","author":"X Li","year":"2007","unstructured":"Li, X. et al. Degradation of HER2 by Cbl-based chimeric ubiquitin ligases. Cancer research 67, 8716\u20138724 (2007).","journal-title":"Cancer research"},{"key":"BFsrep28352_CR33","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1016\/j.canlet.2014.12.043","volume":"359","author":"D Zhong","year":"2015","unstructured":"Zhong, D. et al. Chimeric ubiquitin ligases inhibit non-small cell lung cancer via negative modulation of EGFR signaling. Cancer letters 359, 57\u201364 (2015).","journal-title":"Cancer letters"},{"key":"BFsrep28352_CR34","doi-asserted-by":"crossref","first-page":"4945","DOI":"10.18632\/oncotarget.2066","volume":"5","author":"Q Wang","year":"2014","unstructured":"Wang, Q. et al. Engineered ubiquitin ligase PTB-U-box targets insulin\/insulin-like growth factor receptor for degradation and coordinately inhibits cancer malignancy. Oncotarget 5, 4945\u20134958 (2014).","journal-title":"Oncotarget"},{"key":"BFsrep28352_CR35","doi-asserted-by":"crossref","first-page":"664","DOI":"10.1182\/blood.V96.2.664","volume":"96","author":"RP Million","year":"2000","unstructured":"Million, R. P. & Van Etten, R. A. The Grb2 binding site is required for the induction of chronic myeloid leukemia-like disease in mice by the Bcr\/Abl tyrosine kinase. Blood 96, 664\u2013670 (2000).","journal-title":"Blood"},{"key":"BFsrep28352_CR36","doi-asserted-by":"crossref","first-page":"861","DOI":"10.1016\/j.biocel.2012.02.008","volume":"44","author":"Z Peng","year":"2012","unstructured":"Peng, Z. et al. Targeting BCR tyrosine177 site with novel SH2-DED causes selective leukemia cell death in vitro and in vivo. The international journal of biochemistry & cell biology 44, 861\u2013868 (2012).","journal-title":"The international journal of biochemistry & cell biology"},{"key":"BFsrep28352_CR37","doi-asserted-by":"crossref","first-page":"2038","DOI":"10.1182\/blood.V83.8.2038.2038","volume":"83","author":"A Bedi","year":"1994","unstructured":"Bedi, A., Zehnbauer, B. A., Barber, J. P., Sharkis, S. J. & Jones, R. J. Inhibition of apoptosis by BCR-ABL in chronic myeloid leukemia. Blood 83, 2038\u20132044 (1994).","journal-title":"Blood"},{"key":"BFsrep28352_CR38","doi-asserted-by":"crossref","first-page":"2269","DOI":"10.1182\/blood.V96.6.2269","volume":"96","author":"F Gesbert","year":"2000","unstructured":"Gesbert, F. & Griffin, J. D. Bcr\/Abl activates transcription of the Bcl-X gene through STAT5. Blood 96, 2269\u20132276 (2000).","journal-title":"Blood"},{"key":"BFsrep28352_CR39","doi-asserted-by":"crossref","unstructured":"Adachi, S., Leoni, L. M., Carson, D. A. & Nakahata, T. Apoptosis induced by molecular targeting therapy in hematological malignancies. Acta haematologica 111 (2004).","DOI":"10.1159\/000074490"},{"key":"BFsrep28352_CR40","doi-asserted-by":"crossref","first-page":"8804","DOI":"10.1038\/sj.onc.1206028","volume":"21","author":"M Huang","year":"2002","unstructured":"Huang, M. et al. Inhibition of Bcr-Abl kinase activity by PD180970 blocks constitutive activation of Stat5 and growth of CML cells. Oncogene 21, 8804\u20138816 (2002).","journal-title":"Oncogene"},{"key":"BFsrep28352_CR41","doi-asserted-by":"publisher","first-page":"505","DOI":"10.1203\/PDR.0b013e3181d35017","volume":"67","author":"KM Sakamoto","year":"2010","unstructured":"Sakamoto, K. M. Protacs for treatment of cancer. Pediatr Res 67, 505\u2013508, 10.1203\/PDR.0b013e3181d35017 (2010).","journal-title":"Pediatr Res"},{"key":"BFsrep28352_CR42","doi-asserted-by":"crossref","first-page":"986","DOI":"10.1038\/onc.2013.33","volume":"33","author":"F Kong","year":"2014","unstructured":"Kong, F. et al. Engineering a single ubiquitin ligase for the selective degradation of all activated ErbB receptor tyrosine kinases. Oncogene 33, 986\u2013995 (2014).","journal-title":"Oncogene"},{"key":"BFsrep28352_CR43","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1016\/j.cbpa.2004.10.012","volume":"9","author":"P Zhou","year":"2005","unstructured":"Zhou, P. Targeted protein degradation. Curr Opin Chem Biol 9, 51\u201355 (2005).","journal-title":"Curr Opin Chem Biol"},{"key":"BFsrep28352_CR44","doi-asserted-by":"publisher","first-page":"1966","DOI":"10.1002\/anie.201507978","volume":"55","author":"M Toure","year":"2016","unstructured":"Toure, M. & Crews, C. M. Small-Molecule PROTACS: New Approaches to Protein Degradation. Angew Chem Int Ed Engl 55, 1966\u20131973, 10.1002\/anie.201507978 (2016).","journal-title":"Angew Chem Int Ed Engl"},{"key":"BFsrep28352_CR45","doi-asserted-by":"crossref","first-page":"611","DOI":"10.1038\/nchembio.1858","volume":"11","author":"DP Bondeson","year":"2015","unstructured":"Bondeson, D. P. et al. Catalytic in vivo protein knockdown by small-molecule PROTACs. Nat Chem Biol 11, 611\u2013617 (2015).","journal-title":"Nat Chem Biol"},{"key":"BFsrep28352_CR46","doi-asserted-by":"crossref","first-page":"7201","DOI":"10.1038\/onc.2008.320","volume":"27","author":"A Rodriguez-Gonzalez","year":"2008","unstructured":"Rodriguez-Gonzalez, A. et al. Targeting steroid hormone receptors for ubiquitination and degradation in breast and prostate cancer. Oncogene 27, 7201\u20137211 (2008).","journal-title":"Oncogene"},{"key":"BFsrep28352_CR47","doi-asserted-by":"crossref","first-page":"755","DOI":"10.1016\/j.chembiol.2015.05.009","volume":"22","author":"J Lu","year":"2015","unstructured":"Lu, J. et al. Hijacking the E3 Ubiquitin Ligase Cereblon to Efficiently Target BRD4. Chem Biol 22, 755\u2013763 (2015).","journal-title":"Chem Biol"},{"key":"BFsrep28352_CR48","doi-asserted-by":"crossref","first-page":"807","DOI":"10.1002\/anie.201507634","volume":"55","author":"AC Lai","year":"2016","unstructured":"Lai, A. C. et al. Modular PROTAC Design for the Degradation of Oncogenic BCR-ABL. Angew Chem Int Ed Engl 55, 807\u2013810 (2016).","journal-title":"Angew Chem Int Ed Engl"},{"key":"BFsrep28352_CR49","doi-asserted-by":"crossref","first-page":"7874","DOI":"10.1158\/0008-5472.CAN-05-1581","volume":"65","author":"S Hatakeyama","year":"2005","unstructured":"Hatakeyama, S., Watanabe, M., Fujii, Y. & Nakayama, K. I. Targeted destruction of c-Myc by an engineered ubiquitin ligase suppresses cell transformation and tumor formation. Cancer Res 65, 7874\u20137879 (2005).","journal-title":"Cancer Res"},{"key":"BFsrep28352_CR50","doi-asserted-by":"crossref","first-page":"286","DOI":"10.1158\/1535-7163.MCT-12-0650","volume":"12","author":"Y Ma","year":"2013","unstructured":"Ma, Y. et al. Targeted Degradation of KRAS by an Engineered Ubiquitin Ligase Suppresses Pancreatic Cancer Cell Growth in vitro and in vivo. Mol Cancer Ther 12, 286\u2013294 (2013).","journal-title":"Mol Cancer Ther"},{"key":"BFsrep28352_CR51","doi-asserted-by":"crossref","first-page":"4","DOI":"10.1053\/shem.2003.50034","volume":"40","author":"M Sattler","year":"2003","unstructured":"Sattler, M. & Griffin, J. D. Molecular mechanisms of transformation by the BCR-ABL oncogene. Semin Hematol 40, 4\u201310 (2003).","journal-title":"Semin Hematol"},{"key":"BFsrep28352_CR52","first-page":"553","volume":"36","author":"X Bao","year":"2015","unstructured":"Bao, X. et al. The prognostic value of early BCR-ABL transcripts level in 251 patients with chronic myeloid leukemia after treatment with imatinib. Zhonghua xue ye xue za zhi\u2009=\u2009Zhonghua xueyexue zazhi 36, 553\u2013558 (2015).","journal-title":"Zhonghua xue ye xue za zhi\u2009=\u2009Zhonghua xueyexue zazhi"},{"key":"BFsrep28352_CR53","doi-asserted-by":"crossref","first-page":"428","DOI":"10.1016\/j.ccr.2014.07.006","volume":"26","author":"MS Zabriskie","year":"2014","unstructured":"Zabriskie, M. S. et al. BCR-ABL1 compound mutations combining key kinase domain positions confer clinical resistance to ponatinib in Ph chromosome-positive leukemia. Cancer Cell 26, 428\u2013442 (2014).","journal-title":"Cancer Cell"},{"key":"BFsrep28352_CR54","doi-asserted-by":"crossref","first-page":"21683","DOI":"10.1073\/pnas.1016311108","volume":"107","author":"JH Mao","year":"2010","unstructured":"Mao, J. H. et al. As4S4 targets RING-type E3 ligase c-CBL to induce degradation of BCR-ABL in chronic myelogenous leukemia. Proceedings of the National Academy of Sciences of the United States of America 107, 21683\u201321688 (2010).","journal-title":"Proceedings of the National Academy of Sciences of the United States of America"},{"key":"BFsrep28352_CR55","doi-asserted-by":"crossref","first-page":"3378","DOI":"10.1073\/pnas.0813142106","volume":"106","author":"QY Zhang","year":"2009","unstructured":"Zhang, Q. Y. et al. A systems biology understanding of the synergistic effects of arsenic sulfide and Imatinib in BCR\/ABL-associated leukemia. Proceedings of the National Academy of Sciences of the United States of America 106, 3378\u20133383 (2009).","journal-title":"Proceedings of the National Academy of Sciences of the United States of America"},{"key":"BFsrep28352_CR56","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1016\/j.canlet.2014.12.043","volume":"359","author":"D Zhong","year":"2015","unstructured":"Zhong, D. et al. Chimeric ubiquitin ligases inhibit non-small cell lung cancer via negative modulation of EGFR signaling. Cancer Lett 359, 57\u201364 (2015).","journal-title":"Cancer Lett"}],"container-title":["Scientific Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/srep28352","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/srep28352.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/srep28352.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,1,4]],"date-time":"2023-01-04T17:14:19Z","timestamp":1672852459000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/srep28352"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2016,6,22]]},"references-count":56,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2016,9,13]]}},"alternative-id":["BFsrep28352"],"URL":"https:\/\/doi.org\/10.1038\/srep28352","relation":{},"ISSN":["2045-2322"],"issn-type":[{"value":"2045-2322","type":"electronic"}],"subject":[],"published":{"date-parts":[[2016,6,22]]},"assertion":[{"value":"2 February 2016","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"2 June 2016","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"22 June 2016","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare no competing financial interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"28352"}}