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dc.contributor.authorQiu, JJen_US
dc.contributor.authorLu, Xen_US
dc.contributor.authorZeisig, BBen_US
dc.contributor.authorMa, Zen_US
dc.contributor.authorCai, Xen_US
dc.contributor.authorChen, Sen_US
dc.contributor.authorGronemeyer, Hen_US
dc.contributor.authorTweardy, DJen_US
dc.contributor.authorSo, CWEen_US
dc.contributor.authorDong, Sen_US
dc.date.accessioned2018-08-24T08:25:20Z
dc.date.issued2010-01-21en_US
dc.identifier3en_US
dc.identifier.citationBLOOD, 2010, 115 pp. 643 - 652en_US
dc.identifier.issn0006-4971en_US
dc.identifier.urihttps://repository.icr.ac.uk/handle/internal/2377
dc.identifier.doi10.1182/blood-2009-07-232652en_US
dc.description.abstractPRKAR1A (R1A)-retinoic acid receptor-alpha (R1A-RAR alpha) is the sixth RAR alpha-containing fusion protein in acute promyelocytic leukemia (APL). Using the murine bone-marrow retroviral transduction/transformation assay, we showed that R1A-RAR alpha fusion protein could transform bone-marrow progenitor/stem cells. In gel-shift assays, R1A-RAR alpha was able to bind to a panel of retinoic acid response elements both as a homodimer and as a heterodimer with RXR alpha, and demonstrated distinct DNA-binding characteristics compared with wild-type RAR alpha/RXR alpha or other X-RAR alpha chimeric proteins. The ratio of R1A-RAR alpha to RXR alpha proteins affected the retinoic acid response element interaction pattern of R1A-RAR alpha/RXR alpha complexes. Studies comparing R1A-RAR alpha with R1A-RAR alpha(Delta RIIa) demonstrated that the RIIa protein interaction domain located within R1A was responsible for R1A-RAR alpha homodimeric DNA binding and interaction with wild-type R1A protein. However, the RIIa domain was not required for R1A-RAR alpha-mediated transformation because its deletion in R1A-RAR alpha(Delta RIIa) did not compromise its transformation capability. In contrast, introduction of point mutations within the RAR alpha portion of either R1A-RAR alpha or R1A-RAR alpha(Delta RIIa), previously demonstrated to eliminate RXR alpha interaction or treatment of transduced cells with RXR alpha shRNA or a RXR alpha agonist, reduced transformation capability. Thus, leukemic transformation by APL fusion protein PRKAR1A-RAR alpha is critically dependent on RXR alpha, which suggests RXR alpha is a promising target for APL. (Blood. 2010; 115: 643-652)en_US
dc.format.extent643 - 652en_US
dc.languageEnglishen_US
dc.language.isoEnglishen_US
dc.publisherAMER SOC HEMATOLOGYen_US
dc.titleLeukemic transformation by the APL fusion protein PRKAR1A-RAR alpha critically depends on recruitment of RXR alphaen_US
dc.typeJournal Article
rioxxterms.versionofrecord10.1182/blood-2009-07-232652en_US
rioxxterms.licenseref.startdate2010-01-21en_US
rioxxterms.typeJournal Article/Reviewen_US
dc.relation.isPartOfBLOODen_US
pubs.notesaffiliation: Dong, S (Reprint Author), Baylor Coll Med, Dept Med, 1 Baylor Plaza,BCM 286,Room N1317-03, Houston, TX 77030 USA. Qiu, Jihui J.; Lu, Xiaoxi; Tweardy, David J.; Dong, Shuo, Baylor Coll Med, Dept Med, Houston, TX 77030 USA. Lu, Xiaoxi; Ma, Zhigui, Sichuan Univ, Dept Pediat Hematol, W China Univ Hosp 2, Chengdu 610064, Peoples R China. Zeisig, Bernd B.; So, Chi Wai Eric, Inst Canc Res, Haematooncol Sect, Sutton, Surrey, England. Zeisig, Bernd B.; So, Chi Wai Eric, Kings Coll London, Dept Haematol Med, London WC2R 2LS, England. Cai, Xun; Chen, Saijuan, Shanghai Jiao Tong Univ, Sch Med, State Key Lab Med Genom, Rui Jin Hosp, Shanghai 200030, Peoples R China. Cai, Xun; Chen, Saijuan, Shanghai Jiao Tong Univ, Sch Med, Shanghai Inst Hematol, Rui Jin Hosp, Shanghai 200030, Peoples R China. Gronemeyer, Hinrich, ULP, INSERM, CNRS,Dept Canc Biol, Inst Genet & Biol Mol & Cellulaire,IGBMC, Strasbourg, France. keywords-plus: ACUTE PROMYELOCYTIC LEUKEMIA; RETINOIC ACID RECEPTOR; STAT3 SIGNALING PATHWAYS; NUMA-RAR-ALPHA; REGULATORY SUBUNIT; CROSS-TALK; INTRANUCLEAR MOBILITY; DECREASED MOBILITY; CELL MATURATION; IN-VIVO research-areas: Hematology web-of-science-categories: Hematology author-email: [email protected] researcherid-numbers: Gronemeyer, Hinrich/H-7002-2016 Gronemeyer, Hinrich/G-6240-2011 orcid-numbers: Gronemeyer, Hinrich/0000-0001-9454-2449 Gronemeyer, Hinrich/0000-0001-9454-2449 funding-acknowledgement: Albert and Margaret Alkek Foundation; Kay Kendall Leukemia Fund; Medical Research Council [G0800892] funding-text: The authors thank Dr M. Mavrakis (Cell Biology and Metabolism Branch, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD) for kindly providing the GFP-PRKAR1A expression vector, which facilitated our making a series of R1A and R1A-RAR alpha expression vectors; and Dr M. Busslinger from Research Institute of Molecular Pathology, Vienna, Austria, for the PAX5 expression vector.; This work was supported in part by the Albert and Margaret Alkek Foundation (J.J.Q., S.D.) and the Kay Kendall Leukemia Fund (B.B.Z., C.W.E.S.). number-of-cited-references: 36 times-cited: 15 usage-count-last-180-days: 0 usage-count-since-2013: 1 journal-iso: Blood doc-delivery-number: 546OR unique-id: ISI:000273820600026 oa: gold_or_bronze da: 2018-08-23en_US
pubs.notesNot knownen_US
pubs.organisational-group/ICR
pubs.volume115en_US
pubs.embargo.termsNot knownen_US
dc.contributor.icrauthorZeisig, Bernden_US


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