Article
Cell Biology
Qiang Fang, Xue-Lin Chen, Lei Zhang, Ya-Bin Li, Tian-Zeng Sun, Chen-Xin Yang, Jian-Feng Chang, Xiao-Mei Yang, Feng Sun
Summary: MPS1 is crucial for spermatogenesis, and its absence may lead to cell loss and meiosis blockage during spermatogenesis. MPS1 plays a key role in the formation of sperms and fertility.
CELL DEATH & DISEASE
(2021)
Article
Physiology
Maria-Alexa Cosma, Natalie L. Curtis, Charlotte Pain, Verena Kriechbaumer, Victor M. Bolanos-Garcia
Summary: This study investigates the structure and function of plant CDC20, a key regulator of APC/C in mitosis. The research reveals the presence of conserved protein degradation sites in AtCDC20, similar to other eukaryotes, but also identifies unique features and evolutionary processes in plant species.
FRONTIERS IN PHYSIOLOGY
(2022)
Article
Oncology
Owen J. Chen, Ester Castellsague, Mohamed Moustafa-Kamal, Javad Nadaf, Barbara Rivera, Somayyeh Fahiminiya, Yilin Wang, Isabelle Gamache, Caterina Pacifico, Lai Jiang, Jian Carrot-Zhang, Leora Witkowski, Albert M. Berghuis, Stefan Schoenberger, Dominik Schneider, Morten Hillmer, Susanne Bens, Reiner Siebert, Colin J. R. Stewart, Ziguo Zhang, William C. H. Chao, Celia M. T. Greenwood, David Barford, Marc Tischkowitz, Jacek Majewski, William D. Foulkes, Jose G. Teodoro
Summary: Two germline CDC20 missense variants that segregate with cancer in two families compromise the spindle assembly checkpoint and lead to aberrant mitotic progression, which could predispose cells to transformation.
Article
Biochemistry & Molecular Biology
Yangge Du, Min Zhang, Xuejiao Liu, Zheng Li, Menglong Hu, Yueming Tian, Longwei Lv, Xiao Zhang, Yunsong Liu, Ping Zhang, Yongsheng Zhou
Summary: CDC20, in addition to its well-known role in cell cycle regulation, plays a crucial role in osteogenic commitment of BMSCs. It governs bone formation through regulating ubiquitination and degradation of p65, and knockdown of p65 rescues bone loss in Cdc20 conditional knockout mice.
Article
Biochemistry & Molecular Biology
Kazuyuki Fujimitsu, Hiroyuki Yamano
Summary: The study reveals an interplay between PLK1 enzyme and PP2A-B56 phosphatase on the Apc1 subunit of the APC/C, controlling its activity and mitotic progression through phosphorylation-dependent feedback regulation. PLK1 promotes the formation of APC/C-Cdc20 via phosphorylation, while PP2A-B56 promotes dissociation of PLX1 through dephosphorylation, ultimately regulating the activity and phosphorylation status of APC/C.
Article
Biochemistry & Molecular Biology
Elyse S. Fischer
Summary: The spindle assembly checkpoint (SAC) is a surveillance mechanism in cells that ensures accurate chromosome segregation during mitosis. It delays mitotic exit until all sister chromatid pairs have attached to the bipolar mitotic spindle. The formation of the mitotic checkpoint complex (MCC) is regulated by a phosphorylation signaling cascade and a catalytic scaffold.
Article
Biology
Richard Wang, Camilla Ascanelli, Ahmed Abdelbaki, Alex Fung, Tim Rasmusson, Iacovos Michaelides, Karen Roberts, Catherine Lindon
Summary: In this study, a PROTAC derivative of AURKA inhibitor MLN8237 was characterized for its efficient and specific destruction of AURKA. The subcellular localization and differential sensitivity of AURKA pools to PROTAC action were demonstrated, highlighting the potential of this new class of degrader compounds for targeting specific subpopulations within cells. The findings suggest that PROTACs can modulate AURKA functions in distinct cellular compartments, providing a novel approach for therapeutic intervention.
COMMUNICATIONS BIOLOGY
(2021)
Article
Multidisciplinary Sciences
Pablo Lara-Gonzalez, Taekyung Kim, Karen Oegema, Kevin Corbett, Arshad Desai
Summary: During cell division, kinetochores play a crucial role in protecting chromosomes from aberrations through catalyzing the assembly of Mad2 and Cdc20, forming a diffusible checkpoint complex. This catalysis occurs through a tripartite mechanism involving localized delivery of substrates and phosphorylation-dependent interactions. These findings shed light on how unattached kinetochores generate a signal to safeguard genome integrity during mitosis.
Review
Biochemistry & Molecular Biology
Scott C. Schuyler, Hsin-Yu Chen
Summary: Research on budding yeast Saccharomyces cerevisiae has provided important insights into highly conserved biological pathways, particularly in relation to the mitotic cell cycle and cell cycle checkpoints. Understanding these mechanisms has led to the development of potential drug targets for cancer treatment, such as specific regions in the APC/C subunits and Cdc20, to potentially inhibit mitotic slippage in cancer cells resistant to mitotic poisons.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Multidisciplinary Sciences
Christopher Thomas, Benjamin Wetherall, Mark D. Levasseur, Rebecca J. Harris, Scott T. Kerridge, Jonathan M. G. Higgins, Owen R. Davies, Suzanne Madgwick
Summary: The study reveals an excess of securin over separase in mouse oocytes during meiosis I, with a mechanism promoting securin destruction in prometaphase I. This destruction mechanism relies on specific residues within securin that are exposed when not bound to separase. The authors suggest that this mechanism is crucial for successful meiotic progression in mouse oocytes by ensuring the removal of non-separase-bound securin before metaphase.
NATURE COMMUNICATIONS
(2021)
Article
Oncology
Saki Ota, Yui Tanaka, Ryuji Yasutake, Yuki Ikeda, Ryuzaburo Yuki, Yuji Nakayama, Youhei Saito
Summary: Heat shock can lead to protein denaturation and inactivation in cells. Previous research showed that mild heat shock at 42°C can delay mitotic progression by activating the spindle assembly checkpoint (SAC). However, it is unclear if SAC activation occurs at temperatures higher than 42°C. This study demonstrated that a high temperature of 44°C before mitotic entry caused a prolonged mitotic delay, which was shortened by the SAC inhibitor, AZ3146. Mitotic slippage and multinucleation were observed at 44°C but not at 42°C heat shock. Heat shock at 44°C also reduced the kinetochore localization of MAD2, an important protein for mitotic checkpoint activation, in nocodazole-arrested mitotic cells. These findings suggest that heat shock at 44°C can cause SAC inactivation even after full activation and may lead to mitotic slippage and multinucleation. This has implications for cancer malignancy as mitotic slippage can cause drug resistance and chromosomal instability.
EXPERIMENTAL CELL RESEARCH
(2023)
Article
Cell Biology
Xiaowei Yan, Nico Stuurman, Susana A. Ribeiro, Marvin E. Tanenbaum, Max A. Horlbeck, Christina R. Liem, Marco Jost, Jonathan S. Weissman, Ronald D. Vale
Summary: A microscopy-based optical enrichment approach was developed for selecting and marking cells displaying specific CRISPR-induced phenotypes, followed by isolation using fluorescence-activated cell sorting (FAG). Automated phenotypic identification and photoactivation of cells were achieved through a plugin developed for the open source software mu Manager, allowing screening of approximately 1.5 million individual cells in 8 hours. This scalable approach facilitated the identification of 14 bona fide hits out of 6,092 sgRNAs targeting 544 genes in terms of their effects on nuclear size regulation.
JOURNAL OF CELL BIOLOGY
(2021)
Article
Cell Biology
Li Chen, Ying-Chun Ouyang, Lin-Jian Gu, Jia-Ni Guo, Zhi-Ming Han, Zhen-Bo Wang, Yi Hou, Heide Schatten, Qing-Yuan Sun
Summary: This study demonstrates the critical role of Septin 9 in mouse oocyte meiotic cell cycle progression. Septin 9 regulates the kinetochore-microtubule connection and SAC protein localization on kinetochores, affecting the MI-AI transition as well as APC/C-CDC20 activity and CCNB1 degradation.
CELL PROLIFERATION
(2023)
Article
Biochemistry & Molecular Biology
Sikai Liu, Xiao Yuan, Ping Gui, Ran Liu, Olanrewaju Durojaye, Donald L. Hill, Chuanhai Fu, Xuebiao Yao, Zhen Dou, Xing Liu
Summary: In mitosis, the interaction between Cyclin B2 and Mad2 guides accurate chromosome segregation through their localization at the kinetochores.
Review
Genetics & Heredity
Christine Greil, Monika Engelhardt, Ralph Waesch
Summary: Cell cycle progression is tightly regulated by various protein kinases and proteolysis to maintain genomic stability. The spindle assembly checkpoint plays a crucial role in ensuring correct chromosome separation during mitosis. The ubiquitin ligase proteolysis is essential for these processes, with Cdh1 and Cdc20 being important regulators associated with tumorigenesis.
FRONTIERS IN GENETICS
(2022)
Review
Biochemistry & Molecular Biology
Daniel O. Warmerdam, Rob M. F. Wolthuis
CHROMOSOME RESEARCH
(2019)
Article
Multidisciplinary Sciences
Henri J. van de Vrugt, Tim Harmsen, Joey Riepsaame, Georgina Alexantya, Saskia E. van Mil, Yne de Vries, Rahmen Bin Ali, Ivo J. Huijbers, Josephine C. Dorsman, Rob M. F. Wolthuis, Hein te Riele
SCIENTIFIC REPORTS
(2019)
Article
Biochemistry & Molecular Biology
Daniel O. Warmerdam, Ignacio Alonso-de Vega, Wouter W. Wiegant, Bram van den Broek, Magdalena B. Rother, Rob M. F. Wolthuis, Raimundo Freire, Haico van Attikum, Rene H. Medema, Veronique A. J. Smits
Article
Oncology
Anne M. van Harten, Jos B. Poell, Marijke Buijze, Arjen Brink, Susanne Wells, C. Rene Leemans, Rob M. F. Wolthuis, Ruud H. Brakenhoff
Article
Oncology
Irma van de Beek, Iris E. Glykofridis, Rob M. F. Wolthuis, Hans J. J. P. Gille, Paul C. Johannesma, Hanne E. J. Meijers-Heijboer, R. Jeroen A. van Moorselaar, Arjan C. Houweling
BRITISH JOURNAL OF CANCER
(2020)
Article
Cell Biology
Bente Benedict, Janne J. M. van Schie, Anneke B. Oostra, Jesper A. Balk, Rob M. F. Wolthuis, Hein te Riele, Job de Lange
DEVELOPMENTAL CELL
(2020)
Article
Multidisciplinary Sciences
Atiq Faramarz, Jesper A. Balk, Janne J. M. van Schie, Anneke B. Oostra, Cherien A. Ghandour, Martin A. Rooimans, Rob M. F. Wolthuis, Job de Lange
Article
Multidisciplinary Sciences
Anne M. van Harten, D. Vicky de Boer, Sanne R. Martens-de Kemp, Marijke Buijze, Sonja H. Ganzevles, Keith D. Hunter, C. Rene Leemans, Victor W. van Beusechem, Rob M. F. Wolthuis, Renee X. de Menezes, Ruud H. Brakenhoff
SCIENTIFIC REPORTS
(2020)
Article
Biophysics
Jeanne E. van Dongen, Johanna T. W. Berendsen, Renske D. M. Steenbergen, Rob M. F. Wolthuis, Jan C. T. Eijkel, Loes Segerink
BIOSENSORS & BIOELECTRONICS
(2020)
Article
Multidisciplinary Sciences
Janne J. M. van Schie, Atiq Faramarz, Jesper A. Balk, Grant S. Stewart, Erika Cantelli, Anneke B. Oostra, Martin A. Rooimans, Joanna L. Parish, Cynthia de Almeida Esteves, Katja Dumic, Ingeborg Barisic, Karin E. M. Diderich, Marjon A. van Slegtenhorst, Mohammad Mahtab, Francesca M. Pisani, Hein te Riele, Najim Ameziane, Rob M. F. Wolthuis, Job de Lange
NATURE COMMUNICATIONS
(2020)
Article
Immunology
Katja Apelt, Susan M. White, Hyun Suk Kim, Jung-Eun Yeo, Angela Kragten, Annelotte P. Wondergem, Martin A. Rooimans, Roman Gonzalez-Prieto, Wouter W. Wiegant, Sebastian Lunke, Daniel Flanagan, Sarah Pantaleo, Catherine Quinlan, Winita Hardikar, Haico van Attikum, Alfred C. O. Vertegaal, Brian T. Wilson, Rob M. F. Wolthuis, Orlando D. Scharer, Martijn S. Luijsterburg
Summary: Two siblings were diagnosed with bi-allelic ERCC1 mutations in their teenage years, leading to significantly reduced NER and ICL repair, resulting in a unique phenotype of short stature, photosensitivity, and progressive liver and kidney dysfunction.
JOURNAL OF EXPERIMENTAL MEDICINE
(2021)
Article
Biology
Iris E. Glykofridis, Jaco C. Knol, Jesper A. Balk, Denise Westland, Thang Pham, Sander R. Piersma, Sinead M. Lougheed, Sepide Derakhshan, Puck Veen, Martin A. Rooimans, Saskia E. van Mil, Franziska Bottger, Pino J. Poddighe, Irma van de Beek, Jarno Drost, Fried Jt Zwartkruis, Renee X. de Menezes, Hanne Ej Meijers-Heijboer, Arjan C. Houweling, Connie R. Jimenez, Rob M. F. Wolthuis
Summary: Disrupting FLCN in human renal tubular epithelial cells activates TFE3 and induces interferon response genes independently of interferon. Loss of FLCN promotes STAT2 recruitment to chromatin and slows cellular proliferation.
Article
Cell Biology
Yana van der Weegen, Klaas de Lint, Diana van den Heuvel, Yuka Nakazawa, Tycho E. T. Mevissen, Janne J. M. van Schie, Marta San Martin Alonso, Daphne E. C. Boer, Roman Gonzalez-Prieto, Ishwarya V. Narayanan, Noud H. M. Klaassen, Annelotte P. Wondergem, Khashayar Roohollahi, Josephine C. Dorsman, Yuichiro Hara, Alfred C. O. Vertegaal, Job de Lange, Johannes C. Walter, Sylvie M. Noordermeer, Mats Ljungman, Tomoo Ogi, Rob M. F. Wolthuis, Martijn S. Luijsterburg
Summary: ELOF1 serves as a missing link that facilitates RNAPII ubiquitylation, driving transcription-coupled repair and preventing replication stress. It acts as a specificity factor that binds and positions CRL4(CSA) for optimal RNAPII ubiquitylation, offering key insights into the molecular mechanisms of TCR.
NATURE CELL BIOLOGY
(2021)
Article
Multidisciplinary Sciences
Khashayar Roohollahi, Yvonne de Jong, Govind Pai, Mohamad Amr Zaini, Klaas de Lint, Daoud Sie, Martin A. Rooimans, Davy Rockx, Elizabeth E. Hoskins, Najim Ameziane, Rob Wolthuis, Hans Joenje, Susanne Wells, Josephine Dorsman
Summary: Head-and-neck squamous cell carcinomas (HNSCCs) are common in patients with Fanconi anemia (FA), and standard chemo-radiation therapy is not well tolerated in these patients. This study aimed to find alternative treatment options for FA-HNSCC by identifying genomic and transcriptomic events associated with the disease. The researchers used sequencing techniques to identify copy-number alterations in FA-HNSCC and found that amplification of 11q22.2 was a prevalent event. They also discovered that a small molecule inhibitor of BIRC2-3 could selectively kill FA tumor cells that overexpressed these genes. The findings suggest that inhibition of BIRC2-3 may be a potential therapeutic approach for FA-HNSCC.
SCIENTIFIC REPORTS
(2022)
Article
Multidisciplinary Sciences
Sara Carvalhal, Ingrid Bader, Martin A. Rooimans, Anneke B. Oostra, Jesper A. Balk, Rene G. Feichtinger, Christine Beichler, Michael R. Speicher, Johanna M. van Hagen, Quinten Waisfisz, Mieke van Haelst, Martijn Bruijn, Alexandra Tavares, Johannes A. Mayr, Rob M. F. Wolthuis, Raquel A. Oliveira, Job de Lange
Summary: BUB1 mutations cause neurodevelopmental disorder with cellular phenotypes similar to other syndromes.