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您的检索式：作者名="Hazrat Ismail"
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| 1 | Mitotic motor CENP-E cooperates with PRC1 in temporal control of central spindle assembly显示文摘Error-free cell division depends on the accurate assembly of the spindle midzone from dynamic spindle microtubules to ensure chromatid segregation during metaphase-anaphase transition.However,the mechanism underlying the key transition from the mitotic spindle to central spindle before anaphase onset remains elusive.Given the prevalence of chromosome instability phenotype in gastric tumorigenesis,we developed a strategy to model context-dependent cell division using a combination of light sheet microscope and 3D gastric organoids.Light sheet microscopic image analyses of 3D organoids showed that CENP-E inhibited cells undergoing aberrant metaphase-anaphase transition and exhibiting chromosome segregation errors during mitosis.Highresolution real-time imaging analyses of 2D cell culture revealed that CENP-E inhibited cells undergoing central spindle splitting and chromosome instability phenotype.Using biotinylated syntelin as an affinity matrix,we found that CENP-E forms a complex with PRC1 in mitotic cells.Chemical inhibition of CENP-E in metaphase by syntelin prevented accurate central spindle assembly by perturbing temporal assembly of PRC1 to the midzone.Thus,CENP-E-mediated PRC1 assembly to the central spindle constitutes a temporal switch to organize dynamic kinetochore microtubules into stable midzone arrays.These findings reveal a previously uncharacterized role of CENP-E in temporal control of central spindle assembly.Since CENP-E is absent from yeast,we reasoned that metazoans evolved an elaborate central spindle organization machinery to ensure accurate sister chromatid segregation during anaphase and cytokinesis. | Xu Liu Leilei Xu Junying Li Phil Y.Yao Wanjuan Wang Hazrat Ismail Haowei Wang Bryce Liao Zhihong Yang Tarsha Ward Ke Ruan Jianchun Zhang Quan Wu Ping He Xia Ding Dongmei Wang Chuanhai Fu Zhen Dou Feng Yan Wenwen Wang Xing Liu Xuebiao Yao | 2020 | Journal of Molecular Cell Biology2020，12，8： | 3 |
| 2 | Mechanisms and regulation underlying membraneless organelle plasticity control显示文摘Evolution has enabled living cells to adopt their structural and functional complexity by organizing intricate cellular compartments,such as membrane-bound and membraneless organelles(MLOs),for spatiotemporal catalysis of physiochemical reactions essential for cell plasticity control.Emerging evidence and view support the notion that MLOs are built by multivalent interactions of biomolecules via phase separation and transition mechanisms.In healthy cells,dynamic chemical modifications regulate MLO plasticity,and reversible phase separation is essential for cell homeostasis.Emerging evidence revealed that aberrant phase separation results in numerous neurodegenerative disorders,cancer,and other diseases.In this review,we provide molecular underpinnings on(i)mechanistic understanding of phase separation,(ii)unifying structural and mechanistic principles that underlie this phenomenon,(iii)various mechanisms that are used by cells for the regulation of phase separation,and(iv)emerging therapeutic and other applications. | Hazrat Ismail Xu Liu Fengrui Yang Junying Li Ayesha Zahid Zhen Dou Xing Liu Xuebiao Yao | 2021 | Journal of Molecular Cell Biology2021，13，4： | 1 |
| 3 | Methylation of PLK1 by SET7/9 ensures accurate kinetochore–microtubule dynamics显示文摘Faithful segregation of mitotic chromosomes requires bi-orientation of sister chromatids, which relies on the sensing of correct attachments between spindle microtubules and kinetochores. Although the mechanisms underlying PLK1 activation have been extensively studied, the regulatory mechanisms that couple PLK1 activity to accurate chromosome segregation are not well understood. In particular, PLK1 is implicated in stabilizing kinetochore–microtubule attachments, but how kinetochore PLK1 activity is regulated to avoid hyperstabilized kinetochore–microtubules in mitosis remains elusive. Here, we show that kinetochore PLK1 kinase activity is modulated by SET7/9 via lysine methylation during early mitosis. The SET7/9-elicited dimethylation occurs at the Lys191 of PLK1, which tunes down its activity by limiting ATP utilization. Overexpression of the non-methylatable PLK1 mutant or chemical inhibition of SET7/9 methyltransferase activity resulted in mitotic arrest due to destabilized kinetochore–microtubule attachments. These data suggest that kinetochore PLK1 is essential for stable kinetochore–microtubule attachments and methylation by SET7/9 promotes dynamic kinetochore–microtubule attachments for accurate error correction. Our findings define a novel homeostatic regulation at the kinetochore that integrates protein phosphorylation and methylation with accurate chromosome segregation for maintenance of genomic stability. | Ruoying Yu Huihui Wu Hazrat Ismail Shihao Du Jun Cao Jianyu Wang Tarsha Ward Fengrui Yang Ping Gui Mahboob Ali Lingluo Chu Fei Mo Qi Wang Youjun Chu Jianye Zang Yun Zhao Mingliang Ye Guowei Fang Peng RChen Zhen Dou Xinjiao Gao Wenwen Wang Xing Liu Xuebiao Yao | 2020 | Journal of Molecular Cell Biology2020，12，6： | 0 |
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