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

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• 作者：Mengmeng Pan ; Qiyao Zhang ; Ping Liu ; Jinyan Huang ; Yueying Wang…
• 关键词：NUP98 ; IQCG ; nuclear export ; NF ; κB ; CRM1
• 刊名：Frontiers of Medicine
• 出版年：2016
• 出版时间：December 2016
• 年：2016
• 卷：10
• 期：4
• 页码：410-419
• 全文大小：
• 刊物主题：Medicine/Public Health, general;
• 出版者：Higher Education Press
• ISSN：2095-0225
• 卷排序：10

文摘

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.