title: Inhibition of the nuclear export of p65 and IQCG in leukemogenesis by NUP98-IQCG.
abstract: NUP98 fuses with approximately 34 different partner genes via translocation in hematological malignancies. Transgenic or retrovirus-mediated bone marrow transplanted mouse models reveal the leukemogenesis of some NUP98-related fusion genes. We previously reported the fusion protein NUP98-IQ motif containing G (IQCG) in a myeloid/T lymphoid bi-phenoleukemia patient with t(3;11) and confirmed its leukemogenic ability. Herein, we demonstrated the association of NUP98-IQCG with CRM1, and found that NUP98-IQCG expression inhibits the CRM1-mediated nuclear export of p65 and enhances the transcriptional activity of nuclear factor-κB. Moreover, IQCG could be entrapped in the nucleus by NUP98-IQCG, and the fusion protein interacts with calmodulin via the IQ motif in a calcium-independent manner. Therefore, the inhibition of nuclear exports of p65 and IQCG might contribute to the leukemogenesis of NUP98-IQCG.
authors.affiliation: State Key Laboratory of Medical Genomics, Shanghai Institute of Hematology, Rui Jin Hospital Affiliated to Shanghai Jiao Tong University (SJTU) School of Medicine, Shanghai, 200025, China.
authors.forename: Mengmeng
authors.initials: M
authors.lastname: Pan
authors.affiliation: State Key Laboratory of Medical Genomics, Shanghai Institute of Hematology, Rui Jin Hospital Affiliated to Shanghai Jiao Tong University (SJTU) School of Medicine, Shanghai, 200025, China.|Institute of Health Sciences, Shanghai Institutes for Biological Sciences and Graduate School, Chinese Academy of Sciences and SJTU School of Medicine, Shanghai, 200025, China.
authors.forename: Qiyao
authors.initials: Q
authors.lastname: Zhang
authors.affiliation: State Key Laboratory of Medical Genomics, Shanghai Institute of Hematology, Rui Jin Hospital Affiliated to Shanghai Jiao Tong University (SJTU) School of Medicine, Shanghai, 200025, China.
authors.forename: Ping
authors.initials: P
authors.lastname: Liu
authors.affiliation: State Key Laboratory of Medical Genomics, Shanghai Institute of Hematology, Rui Jin Hospital Affiliated to Shanghai Jiao Tong University (SJTU) School of Medicine, Shanghai, 200025, China.
authors.forename: Jinyan
authors.initials: J
authors.lastname: Huang
authors.affiliation: State Key Laboratory of Medical Genomics, Shanghai Institute of Hematology, Rui Jin Hospital Affiliated to Shanghai Jiao Tong University (SJTU) School of Medicine, Shanghai, 200025, China. yywang@shsmu.edu.cn.
authors.forename: Yueying
authors.initials: Y
authors.lastname: Wang
authors.affiliation: State Key Laboratory of Medical Genomics, Shanghai Institute of Hematology, Rui Jin Hospital Affiliated to Shanghai Jiao Tong University (SJTU) School of Medicine, Shanghai, 200025, China. sjchen@stn.sh.cn.|Institute of Health Sciences, Shanghai Institutes for Biological Sciences and Graduate School, Chinese Academy of Sciences and SJTU School of Medicine, Shanghai, 200025, China. sjchen@stn.sh.cn.
authors.forename: Saijuan
authors.initials: S
authors.lastname: Chen
mesh_terms: D021581:Active Transport, Cell Nucleus; D000818:Animals; D004195:Disease Models, Animal; D015973:Gene Expression Regulation, Leukemic; D057809:HEK293 Cells; D006801:Humans; D028884:Karyopherins / Q000235:genetics / Q000378:metabolism*; D007938:Leukemia / Q000235:genetics*; D051379:Mice; D028861:Nuclear Pore Complex Proteins / Q000235:genetics / Q000378:metabolism*; D018160:Receptors, Cytoplasmic and Nuclear / Q000235:genetics / Q000378:metabolism*; D051996:Transcription Factor RelA / Q000235:genetics / Q000378:metabolism; D014178:Translocation, Genetic; D000097606:Exportin 1 Protein
chemical_list: D028884:Karyopherins; D028861:Nuclear Pore Complex Proteins; D018160:Receptors, Cytoplasmic and Nuclear; D051996:Transcription Factor RelA; D000097606:Exportin 1 Protein; C465451:Nup98 protein, human; C498143:RELA protein, human
keywords: CRM1; NF-κB; NUP98-IQCG; nuclear export