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Mps1 dimerization and multisite interactions with Ndc80 complex enable responsive spindle assembly checkpoint signaling

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Journal of Molecular Cell Biology 2020年第7期12卷 486-498页

作者： Ping Gui Divine M.Sedzro Xiao Yuan Sikai Liu Mohan Hei Wei Tian Najdat Zohbi Fangwei Wang Yihan Yao felix O.aikhionbare Xinjiao Gao Dongmei Wang Xuebiao Yao Zhen Dou MOE Key Laboratory of Membraneless Organelle and Cellular Dynamics Hefei National Laboratory for Physical Sciences at the MicroscaleSchool of Life SciencesUniversity of Science and Technology of ChinaHefei 230027China Keck Center for Cellular Dynamics and Organoids Plasticity Morehouse School of MedicineAtlantaGA 30310USA Key Laboratory of Molecular Biophysics of the Ministry of Education College of Life Science and TechnologyHuazhong University of Science and TechnologyWuhan 430074China Life Sciences Institute and Innovation Center for Cell Signaling Network Zhejiang UniversityHangzhou 310058China

Error-free mitosis depends on accurate chromosome attachment to spindle microtubules,which is monitored by the spindle assembly checkpoint(SAC)*** an upstream factor of SAC,the precise and dynamic kinetochore localization of Mps1 kinase is critical for initiating and silencing SAC ***,the underlying molecular mechanism remains ***,we demonstrated that the multisite interactions between Mps1 and Ndc80 complex(Ndc80C)govern Mps1 kinetochore ***,we identified direct interaction between Mps1 tetratricopeptide repeat domain and *** further identified that Mps1 C-terminal fragment,which contains the protein kinase domain and C-tail,enhances Mps1 kinetochore ***,Mps1 C-terminal fragment mediates its *** of C-tail attenuates the kinetochore targeting and activity of Mps1,leading to aberrant mitosis due to compromised SAC *** together,our study highlights the importance of Mps1 dimerization and multisite interactions with Ndc80C in enabling responsive SAC signaling.

关键词： mitosis spindle assembly checkpoint kinetochore Mps1 kinase Ndc80 complex

IRE1-RACK1 axis orchestrates ER stress preconditioning-elicited cytoprotection from ischemia/reperfusion injury in liver

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分子细胞生物学报:英文版 2016年第2期8卷 144-156页

作者： Dong Liu Xing Liu Ti Zhou William Yao Jun Zhao Zhigang Zheng Wei Jiang Fengsong Wang felix O.aikhionbare Donald L.Hill Nerimah Emmett Zhen Guo Dongmei Wang Xuebiao Yao Yong Chen Department of Hepatobiliary Surgery Xijing HospitalFourth Military Medical UniversityXi’an 710032China Anhui Key Laboratory of Cellular Dynamics and Hefei National Laboratory for Physical Sciences at Nanoscale Hefei 230027China Atlanta Clinical&Translational Science Institute AtlantaGA 30310USA Department of Pathology Xijing HospitalFourth Military Medical UniversityXi’an 710032China Department of Biochemistry Anhui Medical UniversityHefei 230027China Comprehensive Cancer Center University of Alabama at BirminghamBirminghamAL 35294USA Department of Hepatobiliary Surgery Navy General HospitalBeijing 100048China

Endoplasmic reticulum(ER)stress is involved in ischemic preconditioning that protects various organs from ischemia/reperfusion(I/R)*** established an in vivo ER stress preconditioning model in which tunicamycin was injected into rats before hepatic I/*** hepatic I/R injury,demonstrated by serum aminotransferase level and the ultra-structure of the liver,was alleviated by administration of tunicamycin,which induced ER stress in rat liver by activating inositol-requiring enzyme1(IRE1)andupregulating78 kDaglucose-regulated protein(GRP78).The proteomic identification for IRE1 binders revealed interaction and cooperation among receptor for activated C kinase 1(RACK1),phosphorylated AMPK,and IRE1 under ER stress conditions in a spatiotemporal ***,in vitro ER stress preconditioningwas induced by thapsigargin and tunicamycin in L02 and Hep G2 ***,BCL2 was found to bephosphorylated by IRE1 under ER stress conditions to prevent apoptotic process by activation of *** conclusion,ER stress preconditioning protects against hepatic I/R injury,which is orchestrated by IRE1-RACK1 axis through the activation of *** findings provide novel insights into the molecular pathways underlying ER stress preconditioning-elicited cytoprotective effect against hepatic I/R injury.

关键词： IRE1 RACK1 AMPK BCL2 ER stress preconditioning ischemia/reperfusion injury

PML–LRIF1 interactions form a novel link between promyelocytic leukemia bodies and centromeres

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Journal of Molecular Cell Biology 2023年第6期15卷 68-71页

作者： Junying Li Xiao Yuan Fengrui Yang Jun Cao Chunyue Wang Saima Akram Peng Zou felix aikhionbare Xuejun Li Yong Chen Liangyu Zhang Chuanhai Fu Zhikai Wang Xing Liu Xuebiao Yao MOE Key Laboratory for Membraneless Organelles and Cellular Dynamics Division of Life Sciences and MedicineUniversity of Science and Technology of ChinaHefei 230027China Anhui Key Laboratory for Cellular Dynamics and Chemical Biology Hefei National Research Center for Interdisciplinary Sciences at the MicroscaleHefei 230027China Keck Center for Organoid Plasticity AtlantaGA 30310USA Peking-Tsinghua Center for Life Sciences Peking UniversityBeĳing 100871China Department of Gastroenterology Anhui University of Chinese MedicineHefei 230038China Department of Hepatobiliary Surgery Xĳing HospitalFourth Military Medical UniversityXi’an 710033China

Dear Editor,Promyelocytic leukemia(PML)is the scaffold protein that organizes PML bod-ies,which are nuclear membraneless organelles involved in various biologi-cal processes,including tumor suppres-sion and antiviral responses(Ugge et al.,2022).Early electron microscopic analy-ses revealed contacts between the sur-face of PML bodies and chromatin struc-ture(Corpet et al.,2020).In fact,sev-eral chromatin and cell cycle regulators,such as TIP60,P300,and heterochro-matin protein 1(HP1),are localized in PML bodies in interphase cells(Corpet et al.,2020).

关键词： P300 leukemia

Differential Measurements of Oxidatively Modified Proteins in Colorectal Adenopolyps

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International Journal of Clinical Medicine 2015年第4期6卷 289-299页

作者： Sharifeh Mehrabi Lashanale Wallace Shakeria Cohen Xuebiao Yao felix O. aikhionbare Department of Medicine Morehouse School of Medicine Atlanta USA Department of Physiology Morehouse School of Medicine Atlanta USA

Introduction: Adenopolyps patients have a three-fold higher risk of colon cancer over the general population, which increases to six-fold if the polyps are multiple and with lower survival among African American population. Currently, 6% of CRC can be ascribed to mutations in particular genes. Moreover, the optimal management of patients with colorectal adenopolyps depends on the accuracy of appropriate staging strategies because patients with similar colorectal adenocarcinoma architecture display heterogeneity in the course and outcome of the disease. Oxidative stress, due to an imbalance between reactive oxygen species (ROS) and antioxidant capacities as well as a disruption of redox signaling, causes a wide range of damage to DNA, proteins, and lipids which promote tumor formation. Objective/Method: This study applied spectrophotometric, dinitrophenylhydrazone (DNPH) assay, two-dimensional gel electrophoresis, and western blot analyses to assess the levels of oxidatively modified proteins in 41 pairs of primary colorectal tissues including normal/surrounding, adenopolyps (tubular, tubulovillous, villous, polypvillous) and carcinoma. Analysis of variance (ANOVA) and Student’s t-tests were utilized for the resulting data set. Results: Our data showed that the levels of reactive protein carbonyl groups significantly increased as colorectal adenopolyps progresses to malignancy. No significant differences were found in the levels of carbonyl proteins between gender samples analyzed. For African American patients, there were, relative to Caucasians, 10% higher levels of reactive carbonyls in proteins of tubulovillous tissue samples

关键词： Colorectal Adenopolyps Oxidative Stress Carbonyl Proteins

Dynamic phosphorylation of CENP-N by CDK1 guides accurate chromosome segregation in mitosis

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Journal of Molecular Cell Biology 2023年第6期15卷 53-64页

作者： Ran Liu Zhen Dou Tian Tian Xinjiao Gao Lili Chen Xiao Yuan Chunyue Wang Jiahe Hao Ping Gui McKay Mullen felix aikhionbare Liwen Niu Guoqiang Bi Peng Zou Xuan Zhang Chuanhai Fu Xuebiao Yao Jianye Zang Xing Liu MOE Key Laboratory for Cellular Dynamics&Hefei National Research Center for Interdisciplinary Sciences at the Microscale University of Science and Technology of China School of Life SciencesHefei 230026China CAS Center for Excellence in Molecular and Cell Sciences Anhui Key Laboratory for Cellular Dynamics and Chemical BiologyHefei 230027China Keck Center for Cellular Dynamics Morehouse School of MedicineAtlantaGA 30310USA College of Chemistry and Molecular Engineering Peking UniversityBeĳing 100871China

In mitosis,accurate chromosome segregation depends on the kinetochore,a supermolecular machinery that couples dynamic spin-dle microtubules to centromeric ***,the structure–activity relationship of the constitutive centromere-associated network(CCAN)during mitosis remains *** on our recent cryo-electron microscopic analyses of human CCAN structure,we investigated how dynamic phosphorylation of human CENP-N regulates accurate chromosome *** mass spectrometric analyses revealed mitotic phosphorylation of CENP-N by CDK1,which modulates the CENP-L–CENP-N interaction for accurate chromosome segregation and CCAN *** of CENP-N phosphorylation is shown to prevent proper chromosome alignment and activate the spindle assembly *** analyses provide mechanistic insight into a previously undefined link between the centromere–kinetochore network and accurate chromosome segregation.

关键词： mitosis centromere CENP-N CDK1 phosphorylation

Modeling of COVID-19 disease disparity in gastric organoids reveals the spatiotemporal dynamics of SARS-CoV-2 infectivity

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Journal of Molecular Cell Biology 2022年第2期14卷 80-83页

作者： Wenwen Wang Fengrui Yang Jie Lin Saravanakumar Muthusamy Shihao Du McKay Mullen Fatima Garba Wanjuan Wang Xu Liu Tao Li Zhihong Yang Xia Ding felix aikhionbare Xinjiao Gao Zhikai Wang Xing Liu Xuebiao Yao MOE Key Laboratory for Cellular Dynamics University of Science&Technology of China School of Life SciencesHefei 230027China Keck Center for Organoids Plasticity and Department of Surgery Morehouse School of MedicineAtlantaGA 30310USA Anhui Key Laboratory for Cellular Dynamics&Chemical Biology CAS Center of Excellence in Molecular Cell SciencesHefei 230027China Department of Gastroenterology Beĳing University of Chinese MedicineBeĳing 100081China

Dear Editor,The promptness and continuous expansion of the coronavirus disease 2019(COVID-19)pandemic,elicited by severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)and its variants,has presented an unprecedented impact on human health(WHO Coronavirus(COVID-19)Dashboard,2021).Although vaccination has attenuated the severe symptoms,there is no specific antiviral medication available for preventing the viral spread(Drayman et al.,2021).

关键词： acute respiratory

Article Navigation Syntelin inhibits triple-negative breast cancer cell proliferation and metastasis

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Journal of Molecular Cell Biology 2021年第11期13卷 834-837页

作者： McKay Mullen Fengrui Yang Jun Cao Yang Cao Xu Liu Gee Young Lee Tao Li William Yao Zhihong Yang Jiahai Zhang Kela Johnson felix aikhionbare Yong Chen Xinjiao Gao Dongmei Wang Xia Ding Hadiyah-Nicole Green Xing Liu Xuebiao Yao MOE Key Laboratory for Cellular Dynamics Anhui Key Laboratory for Chemical BiologyCAS Center for Excellence in Molecular Cell ScienceUniversity of Science and Technology of ChinaHefei 230027China Keck Center for Oganoids Plasticity Morehouse School of MedicineAtlantaGA 30310USA Department of Hepatobiliary Surgery Xijing HospitalXi’an 710032China BUCM-USTC Collaborative Center for Parietal Cell Research Beijing University of Chinese MedicineBeijing 100029China Ora Lee Smith Cancer Research Foundation AtlantaGA 30310USA

Dear Editor,The hallmarks of cancer comprise several distinct biological characteristics acquired during the multistep development of human tumors with the unique feature of genomic instability(Shen,2011).These cancer characteristics include sustaining proliferative signaling,evading growth suppressors,resisting cell death,enabling replicative immortality,inducing angiogenesis,and activating invasion and metastasis(Chen et al.,2011;Song et al.,2018).Triple-negative breast cancer(TNBC),an aggressive disease with increased risks for visceral metastases,has a poor prognosis due to unavailable and viable therapeutic targets(Bianchini et al.,2016).A TNBC diagnosis indicates that cancer cells test negative for three key receptors:estrogen receptor,progesterone receptor,and human epidermal growth factor receptor 2(Bianchini et al.,2016).The absence of these three receptors renders existing hormone and targeted therapies ineffective.

关键词： metastasis breast

Acetylation of Nup62 by TIP60 ensures accurate chromosome segregation in mitosis

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Journal of Molecular Cell Biology 2022年第8期14卷 53-66页

作者： Hameed Akbar Jun Cao Dongmei Wang Xiao Yuan Manjuan Zhang Saravanakumar Muthusamy Xiaoyu Song Xu Liu felix aikhionbare Xuebiao Yao Xinjiao Gao Xing Liu MOE Key Laboratory for Cellular Dynamics and School of Life Sciences University of Science and Technology of ChinaHefei 230027China CAS Center for Excellence in Molecular and Cell Sciences Anhui Key Laboratory for Cellular Dynamics and Chemical BiologyHefei 230027China Morehouse School of Medicine AtlantaGA 30310USA

Stable transmission of genetic information during cell division requires faithful mitotic spindle assembly and chromosome *** eukaryotic cells,nuclear envelope breakdown(NEBD)is required for proper chromosome *** a list of mitotic kinases has been implicated in NEBD,how they coordinate their activity to dissolve the nuclear envelope and protein machinery such as nuclear pore complexes was ***,we identified a regulatory mechanism in which Nup62 is acetylated by TIP60 in human cell ***62 is a novel substrate of TIP60,and the acetylation of Lys432 by TIP60 dissolves nucleoporin Nup62-Nup58-Nup54 complex during entry into ***,this acetylation-elicited remodeling of nucleoporin complex promotes the distribution of Nup62 to the mitotic spindle,which is indispensable for orchestrating correct spindle ***,suppression of Nup62 perturbs accurate chromosome segregation during *** results establish a previously uncharacterized regulatory mechanism in which TIP60-elicited nucleoporin dynamics promotes chromosome segregation in mitosis.

关键词： mitosis spindle Nup62 TIP60 acetylation

Phosphorylation of human Sgo1 by NEK2A is essential for chromosome congression in mitosis

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Cell Research 2007年第7期17卷 608-618页

作者： Guosheng Fu1 Xia Ding2,3 Kai Yuan1,2 felix aikhionbare2 Jianhui Yao1 Xin Cai1,2 Kai Jiang1,2 Xuebiao Yao1,21 Laboratory of Cellular Dynamics, Hefei National Laboratory, University of Science & Technology of China, Hefei 230027, China2 Department of Physiology and Cancer Biology Program, Morehouse School of Medicine, Atlanta, GA 30310, USA3 Department of Medicine, Beijing University of Chinese Medicine, Beijing 100029, China Laboratory of Cellular Dynamics Hefei National Laboratory University of Science & Technology of China Hefei China Department of Physiology and Cancer Biology Program Morehouse School of Medicine Atlanta USA Department of Medicine Beijing University of Chinese Medicine Beijing China

Chromosome segregation in mitosis is orchestrated by the interaction of the kinetochore with spindle microtubules. Ourrecent study shows that NEK2A interacts with MAD1 at the kinetochore and possibly functions as a novel integrator ofspindle checkpoint signaling. However, it is unclear how NEK2 A regulates kinetochore-microtubule attachment in *** we show that NEK2A phosphorylates human Sgol and such phosphorylation is essential for faithful chromosomecongression in mitosis. NEK2A binds directly to HsSgol in vitro and co-distributes with HsSgol to the kinetochore ofmitotic cells. Our in vitro phosphorylation experiment demonstrated that HsSgol is a substrate of NEK2A and the phos-phorylation sites were mapped to Ser14and Ser507as judged by the incorporation of32P. Although such phosphorylation isnot required for assembly of HsSgol to the kinetochore, expression of non-phosphorylatable mutant HsSgol perturbedchromosome congression and resulted in a dramatic increase in microtubule attachment errors, including syntelic andmonotelic attachments. These findings reveal a key role for the NEK2A-mediated phosphorylation of HsSgol in orches-trating dynamic kinetochore-microtubule interaction. We propose that NEK2 A-mediated phosphorylation of human Sgolprovides a link between centromeric cohesion and spindle microtubule attachment at the kinetochores.

关键词： Sgo1 NEK2A phosphorylation microtubule kinetochore