Frontiers of Medicine

, Volume 10, Issue 4, pp 410–419 | Cite as

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

Research Article

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.

Keywords

NUP98-IQCG nuclear export NF-κB CRM1 

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Supplementary material

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Table S1 Quantitative RT-PCR primers used in the study

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Copyright information

© Higher Education Press and Springer-Verlag Berlin Heidelberg 2016

Authors and Affiliations

  1. 1.State Key Laboratory of Medical Genomics, Shanghai Institute of HematologyRui Jin Hospital Affiliated to Shanghai Jiao Tong University (SJTU) School of MedicineShanghaiChina
  2. 2.Institute of Health Sciences, Shanghai Institutes for Biological Sciences and Graduate SchoolChinese Academy of Sciences and SJTU School of MedicineShanghaiChina

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