@article{67eb6f26bd244d46a134282b4cf7bfaf,
title = "Dynamic crotonylation of EB1 by TIP60 ensures accurate spindle positioning in mitosis",
abstract = "Spindle position control is essential for cell fate determination and organogenesis. Early studies indicate the essential role of the evolutionarily conserved Gαi/LGN/NuMA network in spindle positioning. However, the regulatory mechanisms that couple astral microtubules dynamics to the spindle orientation remain elusive. Here we delineated a new mitosis-specific crotonylation-regulated astral microtubule–EB1–NuMA interaction in mitosis. EB1 is a substrate of TIP60, and TIP60-dependent crotonylation of EB1 tunes accurate spindle positioning in mitosis. Mechanistically, TIP60 crotonylation of EB1 at Lys66 forms a dynamic link between accurate attachment of astral microtubules to the lateral cell cortex defined by NuMA–LGN and fine tune of spindle positioning. Real-time imaging of chromosome movements in HeLa cells expressing genetically encoded crotonylated EB1 revealed the importance of crotonylation dynamics for accurate control of spindle orientation during metaphase–anaphase transition. These findings delineate a general signaling cascade that integrates protein crotonylation with accurate spindle positioning for chromosome stability in mitosis. [Figure not available: see fulltext.]",
author = "Xiaoyu Song and Fengrui Yang and Xu Liu and Peng Xia and Wu Yin and Zhikai Wang and Yong Wang and Xiao Yuan and Zhen Dou and Kai Jiang and Mingming Ma and Bing Hu and Rui Zhang and Chao Xu and Zhiyong Zhang and Ke Ruan and Ruijun Tian and Lin Li and Tao Liu and Hill, {Donald L.} and Jianye Zang and Xing Liu and Jinsong Li and Jinke Cheng and Xuebiao Yao",
note = "Funding Information: We are grateful to Y. Shi, Y. Chen, Y. Luo, H. Jiang, S. Harris-Hooker and G. Tosini for support, and P. Schultz and I.M. Cheeseman for reagents. This work was supported by the MOST-NSFC grants (nos. 2017YFA0503600, 91854203, 31621002, 91853115, 21922706, 31671405, 32090040 and 2016YFA0100500 to Xing L.; 2016YFA0101202, 31970655 to Z.D., 91953101 to Z.Z. and 92059102 to X.S.); the Strategic Priority Research Program of the Chinese Academy of Sciences (grant no. XDB19040000) to Xing L.; the Ministry of Education (grant nos. IRT_17R102, 20113402130010; YD2070006001 to Xing L.); the Fundamental Research Funds for the Central Universities (grant no. WK2070000194 to Xing L.); Anhui Provincial Natural Science Foundation grant (no. 1908085MC64); and a China Postdoctoral Science Foundation grant (no. 2019M662184) to X.S. The funders had no role in study design, data collection and analysis, decision to publish or preparation of the paper. Publisher Copyright: {\textcopyright} 2021, The Author(s), under exclusive licence to Springer Nature America, Inc.",
year = "2021",
month = dec,
doi = "10.1038/s41589-021-00875-7",
language = "English",
volume = "17",
pages = "1314--1323",
journal = "Nature Chemical Biology",
issn = "1552-4450",
number = "12",
}