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 NUP9...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 CRMl-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.展开更多
基因融合是白血病发生的重要原因之一 ,其中涉及多种不同的基因 ,产生多种不同的致癌效应。 NU P98是一种主要参与调节核内外蛋白质和 RNA转运的基因 ,其野生型不具有致癌能力。但当 NU P98与伴侣基因发生融合后 ,其产物具有恶性转化能...基因融合是白血病发生的重要原因之一 ,其中涉及多种不同的基因 ,产生多种不同的致癌效应。 NU P98是一种主要参与调节核内外蛋白质和 RNA转运的基因 ,其野生型不具有致癌能力。但当 NU P98与伴侣基因发生融合后 ,其产物具有恶性转化能力 ,目前已发现这类伴侣基因有 13种。本文主要综述 NU P98的生物学特征、NU展开更多
基金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 ofExcellence （No. 81123005）, the National Natural Science Foundation of China （Nos. 81222004 and 81170506）, and the Samuel Waxman Cancer Research Foundation Co-PI Program.
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 CRMl-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.
文摘基因融合是白血病发生的重要原因之一 ,其中涉及多种不同的基因 ,产生多种不同的致癌效应。 NU P98是一种主要参与调节核内外蛋白质和 RNA转运的基因 ,其野生型不具有致癌能力。但当 NU P98与伴侣基因发生融合后 ,其产物具有恶性转化能力 ,目前已发现这类伴侣基因有 13种。本文主要综述 NU P98的生物学特征、NU
