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Inhibition of the nuclear export of p65 and IQCG in leukemogenesis by NUP98-IQCG

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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.

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Authors and Affiliations

  1. 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

    Mengmeng Pan, Qiyao Zhang, Ping Liu, Jinyan Huang, Yueying Wang & Saijuan Chen

  2. Institute of Health Sciences, Shanghai Institutes for Biological Sciences and Graduate School, Chinese Academy of Sciences and SJTU School of Medicine, Shanghai, 200025, China

    Qiyao Zhang & Saijuan Chen

Authors
  1. Mengmeng Pan
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  2. Qiyao Zhang
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  3. Ping Liu
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  4. Jinyan Huang
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  5. Yueying Wang
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  6. Saijuan Chen
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Correspondence to Yueying Wang or Saijuan Chen.

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Pan, M., Zhang, Q., Liu, P. et al. Inhibition of the nuclear export of p65 and IQCG in leukemogenesis by NUP98-IQCG. Front. Med. 10, 410–419 (2016). https://doi.org/10.1007/s11684-016-0489-0

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  • DOI: https://doi.org/10.1007/s11684-016-0489-0

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