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mitosis-specific acetylation tunes ran effector binding for chromosome segregation
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نویسنده
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bao x. ,liu h. ,liu x. ,ruan k. ,zhang y. ,zhang z. ,hu q. ,liu y. ,akram s. ,zhang j. ,gong q. ,wang w. ,yuan x. ,li j. ,zhao l. ,dou z. ,tian r. ,yao x. ,wu j. ,shi y.
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منبع
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journal of molecular cell biology - 2018 - دوره : 10 - شماره : 1 - صفحه:18 -32
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چکیده
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Stable transmission of genetic information during cell division requires faithful mitotic spindle assembly and chromosome segregation. the ran gtpase plays a key role in mitotic spindle assembly. however, how the generation of a chemical gradient of ran-gtp at the spindle is coupled to mitotic post-translational modifications has never been characterized. here, we solved the complex structure of ran with the nucleotide release factor mog1 and delineated a novel mitosis-specific acetylation-regulated ran-mog1 interaction during chromosome segregation. our structure-guided functional analyses revealed that mog1 competes with rcc1 for ran binding in a gtp/gdp-dependent manner. biochemical characterization demonstrated that mog1-bound ran prevents rcc1 binding and subsequent gtp loading. surprisingly, ran is a bona fide substrate of tip60, and the acetylation of lys134 by tip60 liberates mog1 from ran binding during mitosis. importantly, this acetylation-elicited switch of ran binding to rcc1 promotes high level of ran-gtp, which is essential for chromosome alignment. these results establish a previously uncharacterized regulatory mechanism in which tip60 provides a homeostatic control of ran-gtp level by tuning ran effector binding for chromosome segregation in mitosis.
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کلیدواژه
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chromosome segregation ,lys134 acetylation ,mitosis ,nmr ,ran-gtp ,tip60
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آدرس
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university of science and technology of china, school of life sciences, hefei national laboratory for physical sciences at microscale, china, university of science and technology of china, school of life sciences, hefei national laboratory for physical sciences at microscale, china, chinese academy of sciences, center of excellence in molecular cell sciences, anhui key laboratory for cellular dynamics and chemical biology, china, university of science and technology of china, school of life sciences, hefei national laboratory for physical sciences at microscale, china, university of science and technology of china, school of life sciences, hefei national laboratory for physical sciences at microscale, china, university of science and technology of china, school of life sciences, hefei national laboratory for physical sciences at microscale, china, university of science and technology of china, school of life sciences, hefei national laboratory for physical sciences at microscale, china, university of science and technology of china, school of life sciences, hefei national laboratory for physical sciences at microscale, china, chinese academy of sciences, center of excellence in molecular cell sciences, anhui key laboratory for cellular dynamics and chemical biology, china, university of science and technology of china, school of life sciences, hefei national laboratory for physical sciences at microscale, china, university of science and technology of china, school of life sciences, hefei national laboratory for physical sciences at microscale, china, chinese academy of sciences, center of excellence in molecular cell sciences, anhui key laboratory for cellular dynamics and chemical biology, china, southern university of science and technology, china, morehouse school of medicine, keck center for molecular imaging, usa, morehouse school of medicine, keck center for molecular imaging, usa, chinese academy of sciences, center of excellence in molecular cell sciences, anhui key laboratory for cellular dynamics and chemical biology, china, southern university of science and technology, china, chinese academy of sciences, center of excellence in molecular cell sciences, anhui key laboratory for cellular dynamics and chemical biology, china, university of science and technology of china, school of life sciences, hefei national laboratory for physical sciences at microscale, china, university of science and technology of china, school of life sciences, hefei national laboratory for physical sciences at microscale, china
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Authors
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