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.

Keywords

NUP98-IQCG / nuclear export / NF-κB / CRM1

References

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Acknowledgements

This work was supported by the National Basic Research Program of China (No. 2013CB966800), Ministry of Health (No.201202003), the Mega-projects of Scientific Research for the 12th Five-Year Plan(No. 2013ZX09303302), the State Key Laboratories Project of Excellence (No. 81123005), the National Natural Science Foundation of China (Nos. 81222004 and 81170506), and the Samuel Waxman Cancer Research Foundation Co-PI Program.

Compliance with ethics guidelines Mengmeng Pan, Qiyao Zhang, Ping Liu, Jinyan Huang, Yueying Wang, and Saijuan Chen declare that they have no conflict of interest. All institutional and national guidelines for the care and use of laboratory animals were followed.

Electronic Supplementary Material

Supplementary material is available in the online version of this article at http://dx.doi.org/10.1007/s11684-016-0489-0 and is accessible for authorized users.

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2016 Higher Education Press and Springer-Verlag Berlin Heidelberg