Editorial Material
Biochemistry & Molecular Biology
Liam P. Cheeseman, Helder Maiato
Summary: The attachment of microtubules to kinetochores causes deformation, leading to intrakinetochore stretching. This phenomenon is proposed to be independent of microtubule-pulling forces and plays a role in efficient spindle assembly checkpoint silencing to prevent chromosomal instability.
Article
Multidisciplinary Sciences
Ana C. Henriques, Patricia M. A. Silva, Bruno Sarmento, Hassan Bousbaa
Summary: Antimitotic drugs can induce cell death by activating the spindle assembly checkpoint, but cancer cells treated with these drugs can escape death through mitotic slippage. By inhibiting SAC silencing and delaying mitotic slippage, the effectiveness of antimitotic drugs can be improved, leading to enhanced cell death. Inhibition of SAC silencing also sensitizes cancer cells to apoptosis-inducing small molecules, suggesting a potential therapeutic strategy for antimitotic therapies.
SCIENTIFIC REPORTS
(2021)
Article
Genetics & Heredity
Anne MacKenzie, Victoria Vicory, Soni Lacefield
Summary: To prevent chromosome mis-segregation, cells activate a surveillance mechanism called the spindle checkpoint. This checkpoint delays the cell cycle if kinetochores are not properly attached to spindle microtubules. While previous studies have shown that mitotic cells can escape from prolonged spindle checkpoint activation through a process called mitotic slippage, it is unclear whether meiotic cells have a similar response. In this study, the researchers compared mitotic and meiotic yeast cells and found that meiotic cells have a shorter spindle checkpoint delay and utilize distinct mechanisms, such as silencing the checkpoint at the kinetochore and slippage, to escape checkpoint signaling.
Article
Physiology
Mathew Bloomfield, Jing Chen, Daniela Cimini
Summary: This study found that differences in mitotic duration can be explained by variations in spindle microtubule densities and sizes of the cell, spindle, and spindle poles. The study suggests that spindle size does not always scale with cell size in mammalian cells, and cell size alone is not sufficient to explain differences in metaphase duration. Only when considering a number of spindle architectural features along with cell size can the kinetics of SAC silencing, and hence mitotic duration, be explained in different clones.
FRONTIERS IN PHYSIOLOGY
(2021)
Article
Cell Biology
Wonkyung Oh, Ting Ting Wu, Seo-Yeon Jeong, Ho Jin You, Jung-Hee Lee
Summary: CtIP plays a critical role in regulating mitosis by interacting with TPX2 to control spindle dynamics and regulate the concentration of Aurora A and microtubule intensity at the spindle poles. Depletion of CtIP may lead to improper execution of mitosis and result in chromosomal instability.
Article
Cell Biology
Diana Campos-Iglesias, Julia M. Fraile, Gabriel Bretones, Alejandro A. Montero, Elena Bonzon-Kulichenko, Jesus Vazquez, Carlos Lopez-Otin, Jose M. P. Freije
Summary: USP49 deubiquitinase is identified as a novel regulator of the spindle checkpoint. Loss of USP49 impairs proliferation and increases aneuploidy in cancer cell lines. USP49-depleted cells can overcome SAC-induced arrest in presence of nocodazole.
CELL DEATH & DISEASE
(2023)
Article
Cell Biology
Inmaculada Ayala, Antonino Colanzi
Summary: The Golgi complex plays a central role in secretory traffic and can form a structure called the Golgi ribbon. The balanced formation and cleavage of membrane tubules connecting the stacks are crucial for cell division and spindle formation.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Da-Jie Deng, Xi Wang, Kai-Ye Yue, Yamei Wang, Quan-Wen Jin
Summary: This study investigated the role of fission yeast PP2A in SAC silencing. The results showed that the absence of two B56 regulatory subunits of PP2A only slightly delayed SAC inactivation. Overexpression of individual PP2A subunits could only slightly suppress the SAC silencing defects in PP1 deletion cells. Therefore, fission yeast PP2A is not a key regulator actively involved in SAC inactivation.
Article
Multidisciplinary Sciences
Long Bai, Yu Xiang, Minyue Tang, Shuangying Liu, Qingqing Chen, Qichao Chen, Min Zhang, Shan Wan, Yimiao Sang, Qingfang Li, Sisi Wang, Zhekun Li, Yang Song, Xiaoling Hu, Luna Mao, Guofang Feng, Long Cui, Yinghui Ye, Yimin Zhu
Summary: ALKBH5 plays a crucial role in oocytes by maintaining and stabilizing maternal RNA. It regulates m6A dynamics through demethylation and ensures timely degradation of maternal RNA. Depletion of ALKBH5 leads to defects in oocyte meiosis and female infertility, while the involvement of IGF2BP2 further affects RNA clearance functions.
NATURE COMMUNICATIONS
(2023)
Article
Biochemistry & Molecular Biology
Jian Liu, Hongsheng Xue, Chunxiao Li, Xiangyu Chen, Jiannan Yao, Dongkui Xu, Haili Qian
Summary: We identified the subcellular distribution of MTA1 in mitotic cancer cells and its role in inhibiting SAC activation. MTA1 is localized in the spindle apparatus throughout mitosis and interacts with TPR. The MTA1-TPR complex represents a distinct SAC-associated complex separate from the TPR-MAD1/MAD2 complex.
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
(2023)
Article
Biochemistry & Molecular Biology
Babhrubahan Roy, Janice Sim, Simon J. Y. Han, Ajit P. Joglekar
Summary: The study investigates the interaction between Spc105 and Kre28 in budding yeast KTs. The results show that Spc105 and Kre28 localize at the KT with a 1:1 stoichiometry, and their interaction is important for Spc105 turnover and mutual recruitment at the KTs.
Article
Oncology
Hedy L. Kindler, Silvia Novello, Alessandra Bearz, Giovanni L. Ceresoli, Joachim G. J. Aerts, James Spicer, Paul Taylor, Kristiaan Nackaerts, Alastair Greystoke, Ross Jennens, Luana Calabro, Jacobus A. Burgers, Armando Santoro, Susana Cedres, Piotr Serwatowski, Santiago Ponce, Jan P. Van Meerbeeck, Anna K. Nowak, George Biumenschein, Jonathan M. Siegel, Linda Kasten, Karl Koechert, Annette O. Walter, Barrett H. Childs, Cem Elbi, Raffit Hassan, Dean A. Fennell
Summary: In second-line treatment of malignant pleural mesothelioma, the antibody-drug conjugate anetumab ravtansine showed similar safety and no superiority compared to vinorelbine.
Review
Cell Biology
Angela R. R. Bunning, Mohan L. L. Gupta Jr.
Summary: Accurate chromosome segregation is essential for cell and organismal viability. The mitotic spindle, composed mainly of dynamic microtubules, plays a crucial role in this process by forming a bipolar configuration and generating tension across sister kinetochores. Recent advances have shed light on the role of tension as a biophysical signal that ensures accurate chromosome segregation by destabilizing aberrant kinetochore-microtubule attachments and reinforcing correct connections.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Elyse S. Fischer, Conny W. H. Yu, Dom Bellini, Stephen H. McLaughlin, Christian M. Orr, Armin Wagner, Stefan M. Freund, David Barford
Summary: During metaphase, Mps1 kinase initiates the assembly of the mitotic checkpoint complex (MCC) in response to improper kinetochore-microtubule attachments. The Mad1-Mad2 complex is targeted to kinetochores through interaction with the phosphorylated Bub1, promoting efficient MCC assembly. The crystal structure of the interaction between Mad1(CTD) and phosphorylated Bub1(CD1) peptides reveals asymmetry and implications for MCC assembly efficiency.
Article
Cell Biology
Eric M. C. Britigan, Jun Wan, Daniel K. Sam, Sarah E. Copeland, Amber L. Lasek, Laura C. F. Hrycyniak, Lei Wang, Anjon Audhya, Mark E. Burkard, Avtar Roopra, Beth A. Weaver
Summary: The increased expression of Aurora B protein reduces its kinase activity and causes defects in mitosis. The complexes of Aurora B and its binding partner INCENP achieve Aurora B activation through autophosphorylation.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2022)
Article
Oncology
Jermaine Goveia, Katerina Rohlenova, Federico Taverna, Lucas Treps, Lena-Christin Conradi, Andreas Pircher, Vincent Geldhof, Laura P. M. H. de Rooij, Joanna Kalucka, Liliana Sokol, Melissa Garcia-Caballero, Yingfeng Zheng, Junbin Qian, Laure-Anne Teuwen, Shawez Khan, Bram Boeckx, Els Wauters, Herbert Decaluwe, Paul De Leyn, Johan Vansteenkiste, Birgit Weynand, Xavier Sagaert, Erik Verbeken, Albert Wolthuis, Baki Topal, Wouter Everaert, Hanibal Bohnenberger, Alexander Emmert, Dena Panovska, Frederik De Smet, Frank J. T. Staal, Rene J. Mclaughlin, Francis Impens, Vincenzo Lagani, Stefan Vinckier, Massimiliano Mazzone, Luc Schoonjans, Mieke Dewerchin, Guy Eelen, Tobias K. Karakach, Huanming Yang, Jian Wang, Lars Bolund, Lin Lin, Bernard Thienpont, Xuri Li, Diether Lambrechts, Yonglun Luo, Peter Carmeliet
Article
Cell Biology
Maria Giulia Manzione, Jan Rombouts, Mikhail Steklov, Lorenzo Pasquali, Anna Sablina, Lendert Gelens, Junbin Qian, Mathieu Bollen
MOLECULAR BIOLOGY OF THE CELL
(2020)
Article
Genetics & Heredity
Hae-Ock Lee, Yourae Hong, Hakki Emre Etlioglu, Yong Beom Cho, Valentina Pomelle, Ben Van den Bosch, Jasper Vanhecke, Sara Verbandt, Hyekyung Hong, Jae-Woong Min, Nayoung Kim, Hye Hyeon Eum, Junbin Qian, Bram Boeckx, Diether Lambrechts, Petros Tsantoulis, Gert De Hertogh, Woosung Chung, Taeseob Lee, Minae An, Hyun-Tae Shin, Je-Gun Joung, Min-Hyeok Jung, Gunhwan Ko, Pratyaksha Wirapati, Seok Hyung Kim, Hee Cheol Kim, Seong Hyeon Yun, Iain Bee Huat Tan, Bobby Ranjan, Woo Yong Lee, Tae-You Kim, Jung Kyoon Choi, Young-Joon Kim, Shyam Prabhakar, Sabine Tejpar, Woong-Yang Park
Article
Cell Biology
Junbin Qian, Siel Olbrecht, Bram Boeckx, Hanne Vos, Damya Laoui, Emre Etlioglu, Els Wauters, Valentina Pomella, Sara Verbandt, Pieter Busschaert, Ayse Bassez, Amelie Franken, Marlies Vanden Bempt, Jieyi Xiong, Birgit Weynand, Yannick van Herck, Asier Antoranz, Francesca Maria Bosisio, Bernard Thienpont, Giuseppe Floris, Ignace Vergote, Ann Smeets, Sabine Tejpar, Diether Lambrechts
Article
Cell Biology
Els Wauters, Pierre Van Mol, Abhishek Dinkarnath Garg, Sander Jansen, Yannick Van Herck, Lore Vanderbeke, Ayse Bassez, Bram Boeckx, Bert Malengier-Devlies, Anna Timmerman, Thomas Van Brussel, Tina Van Buyten, Rogier Schepers, Elisabeth Heylen, Dieter Dauwe, Christophe Dooms, Jan Gunst, Greet Hermans, Philippe Meersseman, Dries Testelmans, Jonas Yserbyt, Sabine Tejpar, Walter De Wever, Patrick Matthys, Collaborators CONTAGIOUS, Johan Neyts, Joost Wauters, Junbin Qian, Diether Lambrechts
Summary: Single-cell deep-immune profiling revealed that specific T cells in mild COVID-19 patients exhibit active expansion and function, while in critical COVID-19 they remain more naive. Furthermore, the monocyte-to-macrophage trajectories show enrichment of chronic hyperinflammatory monocytes and depletion of anti-inflammatory alveolar macrophages in critical COVID-19.
Article
Biochemistry & Molecular Biology
Ayse Bassez, Hanne Vos, Laurien Van Dyck, Giuseppe Floris, Ingrid Arijs, Christine Desmedt, Bram Boeckx, Marlies Vanden Bempt, Ines Nevelsteen, Kathleen Lambein, Kevin Punie, Patrick Neven, Abhishek D. Garg, Hans Wildiers, Junbin Qian, Ann Smeets, Diether Lambrechts
Summary: The study found that in breast cancer patients, anti-PD1 treatment can lead to clonal expansion of PD1-expressing T cells in a subset of tumors, regardless of tumor subtype. The expansion mainly involves CD8(+) T cells and CD4(+) T cells with distinct immune cell characteristics.
Article
Multidisciplinary Sciences
Veronica Llorens-Rico, Ann C. Gregory, Johan Van Weyenbergh, Sander Jansen, Tina Van Buyten, Junbin Qian, Marcos Braz, Soraya Maria Menezes, Pierre Van Mol, Lore Vanderbeke, Christophe Dooms, Jan Gunst, Greet Hermans, Philippe Meersseman, Yannick Van Herck, Yannick Van Herck, Alexander Wilmer, Michael Casaer, Stephen Rex, Nathalie Lorent, Jonas Yserbyt, Dries Testelmans, Karin Thevissen, Els Wauters, Johan Neyts, Diether Lambrechts, Joost Wauters, Jeroen Raes
Summary: This study examines the respiratory microbiome of COVID-19 patients and finds that confounders such as time in the ICU and type of oxygen support may play a role in the contradictory results of current studies. Mechanical ventilation is associated with changes in bacterial community structure and shifts in oral taxa linked to COVID-19. The presence of oral bacteria physically associated with proinflammatory immune cells in the lower respiratory tract suggests a possible contribution to exacerbated immune responses in severe disease.
NATURE COMMUNICATIONS
(2021)
Article
Cell Biology
Sheng Chen, Wenyu Cui, Zhexu Chi, Qian Xiao, Tianyi Hu, Qizhen Ye, Kaixiang Zhu, Weiwei Yu, Zhen Wang, Chengxuan Yu, Xiang Pan, Siqi Dai, Qi Yang, Jiacheng Jin, Jian Zhang, Mobai Li, Dehang Yang, Qianzhou Yu, Quanquan Wang, Xiafei Yu, Wei Yang, Xue Zhang, Junbin Qian, Kefeng Ding, Di Wang
Summary: The tumor microenvironment (TME) is a unique niche where constant communication within and between intratumoral cellular compartments occurs, with intratumoral high potassium (K+) having a suppressive effect on T cells. However, the impact of this ionic disturbance on innate immunity, as a pan-cancer characteristic associated with local necrosis, is unknown. In this study, the researchers discovered that intratumoral high K+ suppresses the anti-tumor capacity of tumor-associated macrophages (TAMs). The inwardly rectifying K+ channel Kir2.1 was identified as a central modulator of TAM functional polarization in high K+ TME, and its conditional depletion led to TAM repolarization towards an anti-tumor state, thereby enhancing local anti-tumor immunity. Kir2.1 deficiency disrupted electrochemically dependent glutamine uptake, causing TAM metabolic reprogramming from oxidative phosphorylation to glycolysis. Blocking Kir2.1 attenuated both murine tumor and patient-derived xenograft growth. Overall, the findings suggest that Kir2.1 is a determinant and potential therapeutic target for restoring the anti-tumor capacity of TAMs within an ionic-imbalanced TME.
Article
Biotechnology & Applied Microbiology
Flora D'Anna, Laurien Van Dyck, Jieyi Xiong, Hui Zhao, Rebecca Berrens, Junbin Qian, Pawel Bieniasz-Krzywiec, Vikas Chandra, Luc Schoonjans, Jason Matthews, Julie De Smedt, Liesbeth Minnoye, Ricardo Amorim, Sepideh Khorasanizadeh, Qian Yu, Liyun Zhao, Marie De Borre, Savvas N. Savvides, M. Celeste Simon, Peter Carmeliet, Wolf Reik, Fraydoon Rastinejad, Massimiliano Mazzone, Bernard Thienpont, Diether Lambrechts
