NUP98-IQCG在白血病发生过程中对p65和IQCG核输出的抑制作用。
Inhibition of the nuclear export of p65 and IQCG in leukemogenesis by NUP98-IQCG.
作者信息
Pan Mengmeng, Zhang Qiyao, Liu Ping, Huang Jinyan, Wang Yueying, Chen Saijuan
机构信息
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.
出版信息
Front Med. 2016 Dec;10(4):410-419. doi: 10.1007/s11684-016-0489-0. Epub 2016 Dec 23.
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.
在血液系统恶性肿瘤中，NUP98通过易位与大约34种不同的伙伴基因融合。转基因或逆转录病毒介导的骨髓移植小鼠模型揭示了一些NUP98相关融合基因的白血病发生机制。我们之前报道了一名患有t(3;11)的髓系/T淋巴细胞双表型白血病患者中的融合蛋白NUP98-含IQ模体的G蛋白（IQCG），并证实了其致白血病能力。在此，我们证明了NUP98-IQCG与CRM1的关联，发现NUP98-IQCG的表达抑制了CRM1介导的p65核输出，并增强了核因子κB的转录活性。此外，IQCG可被NUP98-IQCG截留在细胞核中，并且该融合蛋白通过IQ模体以不依赖钙的方式与钙调蛋白相互作用。因此，p65和IQCG核输出的抑制可能有助于NUP98-IQCG的白血病发生。
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