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
Biochemistry & Molecular Biology
Fiorella Faienza, Federica Polverino, Girish Rajendraprasad, Giacomo Milletti, Zehan Hu, Barbara Colella, Deborah Gargano, Flavie Strappazzon, Salvatore Rizza, Mette Vixo Vistesen, Yonglun Luo, Manuela Antonioli, Valentina Cianfanelli, Caterina Ferraina, Gian Maria Fimia, Giuseppe Filomeni, Daniela De Zio, Joern Dengjel, Marin Barisic, Giulia Guarguaglini, Sabrina Di Bartolomeo, Francesco Cecconi
Summary: AMBRA1 is a key factor for nervous system development, primarily associated with autophagy and cell proliferation control. This study reveals that AMBRA1 is phosphorylated during mitosis and is critical for spindle function and orientation, driven by NUMA1 protein. The localization and dynamics of NUMA1 are dependent on AMBRA1 presence, phosphorylation, and binding ability. These findings suggest an additional role of AMBRA1 in tissue morphogenesis and differentiation, which could have implications for development and cancer oncogenesis.
CELLULAR AND MOLECULAR LIFE SCIENCES
(2023)
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
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
Biochemistry & Molecular Biology
Yukihiro Sera, Tsuneo Imanaka, Masafumi Yamaguchi
Summary: SDS is a genetic disorder caused by mutations in the SBDS gene, which is involved in ribosome biogenesis. The interaction between SBDS and RNF2 at different stages of the cell cycle may play a role in mitotic progression.
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
(2023)
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
Multidisciplinary Sciences
Emmanuel K. Teye, Shasha Lu, Fangyuan Chen, Wenrui Yang, Thomas Abraham, Douglas B. Stairs, Gregory S. Yochum, Robert A. Brodsky, Jefrey J. Pu
Summary: PIGN, as a regulator of the spindle assembly checkpoint, affects the activation of mitotic checkpoint in leukemic cells, which in turn influences chromosome segregation, suggesting a crucial role in suppressing chromosomal instability associated with leukemia.
SCIENTIFIC REPORTS
(2021)
Article
Biochemistry & Molecular Biology
Jia-Qian Ju, Xiao-Han Li, Meng-Hao Pan, Yi Xu, Yao Xu, Ming-Hong Sun, Shao-Chen Sun
Summary: Mps1 plays crucial roles in regulating the spindle assembly checkpoint and DNA repair during mouse early embryo development. Loss of Mps1 activity leads to abnormal early cleavage, disrupted spindle organization, increased DNA damage, oxidative stress, and activation of apoptosis and autophagy pathways.
JOURNAL OF CELLULAR BIOCHEMISTRY
(2021)
Article
Oncology
Dilara Koyuncu, Utsav Sharma, Erik T. Goka, Marc E. Lippman
Summary: The study revealed that SAC genes were elevated in breast cancer, with BUB1B showing the most significant change. Overexpression of BUB1B was associated with decreased overall survival. Reduction of BUB1B expression led to decreased viability and clonogenicity in BrCa cell lines, increased apoptosis and cell death, as well as chromosomal abnormalities.
BREAST CANCER RESEARCH AND TREATMENT
(2021)
Article
Biology
Dilara Kocakaplan, Huseyin Karaburk, Cansu Dilege, Idil Kirdok, Seyma Nur Bektas, Ayse Koca Caydasi
Summary: In this study, a novel checkpoint component Glc7-Bud14 was identified, which promotes dephosphorylation of the SPOC effector protein Bfa1. The results suggest that two mechanisms act in parallel for a robust checkpoint response, where SPOC kinase Kin4 isolates Bfa1 away from inhibitory kinase Cdc5, and Glc7-Bud14 dephosphorylates Bfa1 to fully activate the checkpoint effector.
Article
Cell Biology
Sebastian Palacios Martinez, Jessica Greaney, Jennifer Zenker
Summary: This review summarizes the recent discoveries on microtubule organization and function during early human embryogenesis and compares them to innovative studies conducted in alternative mammalian models. It highlights the differences and analogies of centriole inheritance and emphasizes the significance of non-centrosomal MTOCs for embryo viability.
CURRENT OPINION IN CELL BIOLOGY
(2022)
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)
Article
Biochemistry & Molecular Biology
Ozge Ozguc, Ludmilla de Plater, Varun Kapoor, Anna Francesca Tortorelli, Andrew G. Clark, Jean-Leon Maitre
Summary: Actomyosin contractility is a major driving force of preimplantation morphogenesis in mouse embryonic development. The appearance of periodic cortical waves of contraction (PeCoWaCo) marks the activation of contractility, which gradually increases in frequency during successive cleavage divisions. The reduction in cell size caused by cleavage divisions does not explain the presence of PeCoWaCo or their accelerating rhythm. Instead, we find that blastomeres gradually decrease their surface tensions until the 8-cell stage, and artificially softening cells enhances PeCoWaCo prematurely. The down-regulation of formin Fmnl3 is identified as a required event to soften the cortex and expose PeCoWaCo, awakening zygotic contractility before preimplantation morphogenesis.
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
Developmental Biology
Marianne Roca, Lydia Besnardeau, Elisabeth Christians, Alex McDougall, Janet Chenevert, Stefania Castagnetti
Summary: The spindle assembly checkpoint (SAC) is responsible for delaying anaphase onset until all chromosomes are correctly attached to spindle microtubules, maintaining genome integrity. In chordate embryos, SAC is inactive or cell-cycle target machinery is unresponsive during early development, allowing mitotic progression despite spindle defects. However, in Phallusia mammillata embryos, the SAC delays mitotic progression from the 8th cleavage divisions and unattached kinetochores are recognized by the SAC machinery after the 7th cell cycle. The strength of SAC and its modulation by cell fate and size resemble SAC control in non-chordate embryos.
Article
Biochemistry & Molecular Biology
Yanchang Wei, Cai-Rong Yang, Yan-Ping Wei, Zhao-Jia Ge, Zhen-Ao Zhao, Bing Zhang, Yi Hou, Heide Schatten, Qing-Yuan Sun
JOURNAL OF BIOLOGICAL CHEMISTRY
(2015)
Article
Endocrinology & Metabolism
Cai-Rong Yang, Katie M. Lowther, Maria D. Lalioti, Emre Seli
Article
Cell Biology
Ye Yang, Cai-Rong Yang, Seung Jin Han, Enrico Maria Daldello, Ara Cho, Joao P. Sousa Martins, Guoliang Xia, Marco Conti
GENES & DEVELOPMENT
(2017)
Article
Cell Biology
Lei Chen, Shi-Bin Chao, Zhen-Bo Wang, Shu-Tao Qi, Xiu-Lan Zhu, Shang-Wu Yang, Cai-Rong Yang, Qing-Hua Zhang, Ying-Chun Ouyang, Yi Hou, Heide Schatten, Qing-Yuan Sun
Article
Cell Biology
Qing-Hua Zhang, Shu-Tao Qi, Zhen-Bo Wang, Cai-Rong Yang, Yanchang Wei, Lei Chen, Ying-Chun Ouyang, Yi Hou, Heide Schatten, Qing-Yuan Sun
Article
Multidisciplinary Sciences
Cai-Rong Yang, Yanchang Wei, Shu-Tao Qi, Lei Chen, Qing-Hua Zhang, Jun-Yu Ma, Yi-Bo Luo, Ya-Peng Wang, Yi Hou, Heide Schatten, Zhong-Hua Liu, Qing-Yuan Sun
Article
Multidisciplinary Sciences
Lei Guo, Shu-Tao Qi, De-Qiang Miao, Xing-Wei Liang, Hui Li, Xiang-Hong Ou, Xin Huang, Cai-Rong Yang, Ying-Chun Ouyang, Yi Hou, Qing-Yuan Sun, Zhiming Han
Article
Multidisciplinary Sciences
Yanchang Wei, Cai-Rong Yang, Yan-Ping Wei, Zhen-Ao Zhao, Yi Hou, Heide Schatten, Qing-Yuan Sun
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2014)
Article
Developmental Biology
Enrico Maria Daldello, Xuan G. Luong, Cai-Rong Yang, Jonathan Kuhn, Marco Conti
Article
Multidisciplinary Sciences
Yanchang Wei, Jingwen Lang, Qian Zhang, Cai-Rong Yang, Zhen-Ao Zhao, Yixin Zhang, Yanzhi Du, Yun Sun
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2019)
Article
Biochemistry & Molecular Biology
Xuan G. Luong, Enrico Maria Daldello, Gabriel Rajkovic, Cai-Rong Yang, Marco Conti
NUCLEIC ACIDS RESEARCH
(2020)
Article
Multidisciplinary Sciences
Cai-Rong Yang, Gabriel Rajkovic, Enrico Maria Daldello, Xuan G. Luong, Jing Chen, Marco Conti
NATURE COMMUNICATIONS
(2020)
Article
Reproductive Biology
Katie M. Lowther, Federico Favero, Cai-Rong Yang, Hugh S. Taylor, Emre Seli
BIOLOGY OF REPRODUCTION
(2017)
Meeting Abstract
Obstetrics & Gynecology
Katie Lowther, Federico Favero, Cairong Yang, Hugh Taylor, Emre Seli
REPRODUCTIVE SCIENCES
(2016)
Meeting Abstract
Obstetrics & Gynecology
Cairong Yang, Emre Seli
REPRODUCTIVE SCIENCES
(2015)