Review
Biochemistry & Molecular Biology
Ni Made Pitri Susanti, Daryono Hadi Tjahjono
Summary: The cell cycle is crucial in cell development, and its progression is controlled by endogenous CDK inhibitors, CDKs, and cyclins. Dysregulation of the cell cycle can lead to cancer, making CDK a natural target for anticancer therapy. Understanding CDK structures and complexes with drugs helps in developing CDK inhibitors, from non-selective to selective CDK4/CDK6 inhibitors applied in clinical cancer treatment.
Article
Multidisciplinary Sciences
N. Tavernier, Y. Thomas, S. Vigneron, P. Maisonneuve, S. Orlicky, P. Mader, S. G. Regmi, L. Van Hove, N. M. Levinson, G. Gasmi-Seabrook, N. Joly, M. Poteau, G. Velez-Aguilera, O. Gavet, A. Castro, M. Dasso, T. Lorca, F. Sicheri, L. Pintard
Summary: The research uncovers the activation mechanism of AURKA crucial for mitotic entry, showing that phosphorylated Bora directly activates AURKA kinase activity. Through specific amino acid regions, Bora binds AURKA and substitutes for a key phospho-regulatory site, highlighting the importance of this mechanism for timely mitotic entry in Xenopus and human cells.
NATURE COMMUNICATIONS
(2021)
Article
Cell Biology
Enric Mocholi, Laura Russo, Keshav Gopal, Andrew G. Ramstead, Sophia M. Hochrein, Harmjan R. Vos, Geert Geeven, Adeolu O. Adegoke, Anna Hoekstra, Robert M. van Es, Jose Ramos Pittol, Sebastian Vastert, Jared Rutter, Timothy Radstake, Jorg van Loosdregt, Celia Berkers, Michal Mokry, Colin C. Anderson, Ryan M. O'Connell, Martin Vaeth, John Ussher, Boudewijn M. T. Burgering, Paul J. Coffer
Summary: Upon antigen-specific TCR engagement, the generation of extramitochondrial pyruvate is crucial for acetyl-CoA production and subsequent histone acetylation remodeling. PDH-deficient T cells show that PDH-dependent acetyl-CoA production is a rate-limiting step during T cell activation. This study highlights the integration of metabolic and histone-modifying enzymes in CD4+ T cell activation, suggesting a potential therapeutic approach for regulating antigen-driven T cell activation.
Article
Cell Biology
Yujia Sun, Yongding Huang, Zhitai Hao, Shoutao Zhang, Qingnan Tian
Summary: Adult stem cells (ASCs) are pluripotent cells that can self-renew and replace lost cells. Understanding the molecular mechanisms of stem cell proliferation and cell fate decision is important for regeneration and homeostasis. In this study, researchers identified a gene called myosin regulatory light chain (MRLC) that plays a crucial role in the development of the planarian epidermis. Knockdown of MRLC leads to increased cell death, abnormal regeneration, and eventually animal death. MRLC is also involved in regulating the proliferation and differentiation of epidermal cells by cooperating with another gene called cdc42.
CELL PROLIFERATION
(2023)
Article
Cell Biology
Timothy Patton, Zhe Zhao, Xin Yi Lim, Eleanor Eddy, Huimeng Wang, Adam G. Nelson, Bronte Ennis, Sidonia B. G. Eckle, Michael N. T. Souter, Troi J. Pediongco, Hui-Fern Koay, Jian-Guo Zhang, Tirta M. Djajawi, Cynthia Louis, Najoua Lalaoui, Nicolas Jacquelot, Andrew M. Lew, Daniel G. Pellicci, James McCluskey, Yifan Zhan, Zhenjun Chen, Kate E. Lawlor, Alexandra J. Corbett
Summary: Cell death mechanisms in T lymphocytes vary depending on their developmental stage, cell subset, and activation status. However, the cell death control mechanisms of mucosal-associated invariant T (MAIT) cells, a specialized T cell population, are not well understood. In this study, it was found that MAIT cells express high levels of key necroptotic machinery, RIPK3 and MLKL proteins. Surprisingly, the loss of RIPK3, but not MLKL or caspase-8, specifically increased the abundance of MAIT cells in various organs, indicating a cell-intrinsic regulation of MAIT cell accumulation by RIPK3 signaling.
CELL DEATH & DISEASE
(2023)
Article
Cell Biology
Lam Ngoc Thao Nguyen, Lam Nhat Nguyen, Juan Zhao, Madison Schank, Xindi Dang, Dechao Cao, Sushant Khanal, Xiao Y. Wu, Yi Zhang, Jinyu Zhang, Shunbin Ning, Ling Wang, Mohamed El Gazzar, Jonathan P. Moorman, Zhi Q. Yao
Summary: This study found that the inhibition of TRF2 expression, rather than telomerase disruption, is responsible for CD4T cell dysfunction in chronic viral infections. Restoring TRF2 may present a novel approach to prevent telomeric DNA damage and premature T-cell aging.
JOURNAL OF CELL SCIENCE
(2022)
Article
Biology
Joseph O. Magliozzi, James B. Moseley
Summary: This study reveals a new role for Pak1 in regulating cell shape through its association with the RNA-binding protein Sts5 and P bodies. Pak1 plays a key role in preventing Sts5 from associating with P bodies and promotes rapid dissolution of Sts5 during glucose addition by localizing to stress granules.
Editorial Material
Multidisciplinary Sciences
Till Klecker, Benedikt Westermann
Summary: Mitochondria, essential organelles in cells, are successfully inherited during cell division through three types of interaction with filaments of actin protein.
Article
Biology
Zain Alhashem, Dylan Feldner-Busztin, Christopher Revell, Macarena Alvarez-Garcillan Portillo, Karen Camargo-Sosa, Joanna Richardson, Manuel Rocha, Anton Gauert, Tatianna Corbeaux, Martina Milanetto, Francesco Argenton, Natascia Tiso, Robert N. Kelsh, Victoria E. Prince, Katie Bentley, Claudia Linker
Summary: Coordination between cell proliferation and migration is crucial for life, and its dysregulation can have catastrophic consequences. This study reveals that the interaction between Notch signaling and cell cycle progression determines the identities of leader and follower cells during migration in zebrafish.
Article
Multidisciplinary Sciences
Jiaxing Chen, Yashavantha L. Vishweshwaraiah, Richard B. Mailman, Erdem D. Tabdanov, Nikolay Dokholyan
Summary: Single-protein-based devices that integrate signal sensing with logical operations have the potential to monitor and modulate biological systems effectively. However, designing intelligent nanoscale computing agents with sensor domains integrated into functional proteins is challenging. In this study, the researchers incorporated a rapamycin-sensitive sensor and a blue light-responsive domain into a human Src kinase, creating a protein device that functions as a noncom-mutative combinatorial logic circuit. By applying the appropriate input signals, this protein device can reversibly control cell orientation, which has implications for tissue engineering and regenerative medicine.
Review
Immunology
Arwa Elaagip, Sabrina Absalon, Anat Florentin
Summary: This article reviews various aspects of organelle dynamics during P. falciparum intracellular replication, summarizes current understanding of these processes, and describes many unanswered questions in this field of parasite basic cell biology.
FRONTIERS IN CELLULAR AND INFECTION MICROBIOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Sung Hoon Lee, Jay C. Hou, Archer Hamidzadeh, M. Sulaiman Yousafzai, Visar Ajeti, Hao Chang, David J. Odde, Michael Murrell, Andre Levchenko
Summary: This study reveals that cyclic changes in the activity of the small GTPase RhoA, mediated by the RhoA guanine nucleotide exchange factor GEF-H1 and triggered by an increase in intracellular Ca2+ levels, are responsible for navigation through a dense extracellular matrix during cell migration. The cyclic changes are driven by two coupled negative feedback loops dependent on microtubule dynamics. Additionally, an increasing frequency of the molecular clock leads to faster cell migration within physically confining spaces.
Review
Cell Biology
Rustem Uzbekov, Claude Prigent
Summary: All living organisms are composed of cells, which undergo cell division to reproduce and form a whole organism. Cell division is a highly regulated process that follows a sequence of events known as the cell cycle. The universality of the cell cycle is attributed to the shared genetic information encoded by the DNA double helix in all organisms.
Review
Genetics & Heredity
Fatemeh Sadoughi, Jamal Hallajzadeh, Zatollah Asemi, Mohammad Ali Mansournia, Forough Alemi, Bahman Yousefi
Summary: Our genome undergoes tens of thousands of harms and damages daily, and cells have sophisticated mechanisms to repair them to maintain genome stability; Cells must sustain the integrity of genetic content, and mediators play a crucial role in transmitting DNA damage signals to prevent defective DNA replication.
Article
Biochemistry & Molecular Biology
Mariana Romeiro Motta, Xin'Ai Zhao, Martine Pastuglia, Katia Belcram, Farshad Roodbarkelari, Maki Komaki, Hirofumi Harashima, Shinichiro Komaki, Manoj Kumar, Petra Bulankova, Maren Heese, Karel Riha, David Bouchez, Arp Schnittger
Summary: Flowering plants contain multiple cyclin families, with B1-type cyclins playing a crucial role in cell cycle control during Arabidopsis development. Mutant analysis revealed complex overlapping requirements of B1-type cyclins, with CYCB1;2 being central. The double mutant cycb1;1 cycb1;2, although compromised in growth, provides a unique opportunity to study the function of B1-type cyclins at the organismic level.
Article
Multidisciplinary Sciences
Phil Ruis, David Van Ly, Valerie Borel, Georgia R. Kafer, Afshan McCarthy, Steven Howell, Robert Blassberg, Ambrosius P. Snijders, James Briscoe, Kathy K. Niakan, Paulina Marzec, Anthony J. Cesare, Simon J. Boulton
Summary: This study demonstrates that in mouse pluripotent embryonic stem cells and epiblast stem cells, TRF2 is largely dispensable for telomere protection, with cells exhibiting an attenuated telomeric DNA damage response and the ability to propagate for multiple generations even in the absence of TRF2. Cells exiting pluripotency rapidly switch to TRF2-dependent end protection, and embryos lacking Trf2 arrest before implantation with evidence of DNA damage response signaling and apoptosis in the non-pluripotent compartment. The formation of T-loops independently of TRF2 in ES cells explains why TRF2 is not essential for end protection during pluripotency.
Article
Respiratory System
Razia Zakarya, Yik L. Chan, Sandra Rutting, Karosham Reddy, Jack Bozier, Roy R. Woldhuis, Dikaia Xenaki, David Van Ly, Hui Chen, Corry-Anke Brandsma, Ian M. Adcock, Brian G. Oliver
Summary: This study aims to determine whether COPD airway smooth muscle cells have a unique epigenetic response to the profibrotic cytokine transforming growth factor beta 1 (TGF-beta 1), indicating a potential link between epigenetic changes and lung fibrosis.
Article
Biochemistry & Molecular Biology
Felix Breyer, Anetta Hartlova, Teresa Thurston, Helen R. Flynn, Probir Chakravarty, Julia Janzen, Julien Peltier, Tiaan Heunis, Ambrosius P. Snijders, Matthias Trost, Steven C. Ley
Summary: TPL-2 kinase mediates TLR activation of MAP kinases to modulate cytokine expression in myeloid cells, and also plays a crucial role in regulating phagosome maturation for efficient killing of phagocytosed microbes.
Article
Biochemical Research Methods
Beatriz Calle, Ganka Bineva-Todd, Andrea Marchesi, Helen Flynn, Mattia Ghirardello, Omur Y. Tastan, Chloe Roustan, Junwon Choi, M. Carmen Galan, Benjamin Schumann, Stacy A. Malaker
Summary: Mucin-type O-glycosylation is a complex post-translational modification that presents challenges for analysis. Recent introduction of chemically modified monosaccharide analogues has improved mass spectrometry analysis of O-glycopeptides, offering opportunities for optimized attributes such as increased charge state and predictable fragmentation behavior.
JOURNAL OF THE AMERICAN SOCIETY FOR MASS SPECTROMETRY
(2021)
Article
Multidisciplinary Sciences
Aurelia C. Balestra, Konstantinos Koussis, Natacha Klages, Steven A. Howell, Helen R. Flynn, Marcus Bantscheff, Carla Pasquarello, Abigail J. Perrin, Lorenzo Brusini, Patrizia Arboit, Olalla Sanz, Laura Peces-Barba Castano, Chrislaine Withers-Martinez, Alexandre Hainard, Sonja Ghidelli-Disse, Ambrosius P. Snijders, David A. Baker, Michael J. Blackman, Mathieu Brochet
Summary: The multipass membrane protein ICM1 is tightly associated with PKG and plays a crucial role in calcium signaling in the malaria parasite. Depletion of ICM1 leads to blocked intracellular calcium mobilization and impacts the parasite's lifecycle transitions and transmission.
Article
Biochemistry & Molecular Biology
Thomas John Mercer, Yohei Ohashi, Stefan Boeing, Harold Bj Jefferies, Stefano De Tito, Helen Flynn, Shirley Tremel, Wenxin Zhang, Martina Wirth, David Frith, Ambrosius P. Snijders, Roger Lee Williams, Sharon A. Tooze
Summary: Autophagy is regulated by ULK and VPS15 through phosphorylation, affecting the formation and activity of autophagosomes. The study reveals the crucial role of VPS15 in autophagy and its association with ULK.
Review
Cell Biology
Noa Lamm, Samuel Rogers, Anthony J. Cesare
Summary: This study focuses on the role of nuclear-specific filamentous actin in mobilizing damaged chromatin in response to DNA double-strand breaks and replication stress, as well as the importance of nuclear pore complexes and promyelocytic leukemia-nuclear bodies as specialized platforms for homology-directed repair. The literature suggests an emerging model where specific types of DNA lesions are subjected to nuclear-derived forces that promote interaction with repair hubs to facilitate specialized repair reactions.
TRENDS IN CELL BIOLOGY
(2021)
Article
Multidisciplinary Sciences
Matthew E. Cockman, Yoichiro Sugimoto, Hamish B. Pegg, Norma Masson, Eidarus Salah, Anthony Tumber, Helen R. Flynn, Joanna M. Kirkpatrick, Christopher J. Schofield, Peter J. Ratcliffe
Summary: JMJD6 is a 2-oxoglutarate-dependent dioxygenase involved in various cellular processes. Through mass spectrometry analysis, we identified 150 lysine hydroxylation sites on 48 protein substrates catalyzed by JMJD6, including 19 hydroxylation sites on BRD4. Most of these substrates are associated with membraneless organelle formation, suggesting a potential role for JMJD6 in regulating subcellular partitioning in response to stress.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Article
Multidisciplinary Sciences
Anna Cioce, Beatriz Calle, Tatiana Rizou, Sarah C. Lowery, Victoria Bridgeman, Keira E. Mahoney, Andrea Marchesi, Ganka Bineva-Todd, Helen Flynn, Zhen Li, Omur Y. Tastan, Chloe Roustan, Pablo Soro-Barrio, Thomas M. Wood, Tessa Keenan, Peter Both, Kun Huang, Fabio Parmeggiani, Ambrosius P. Snijders, Mark Skehel, Svend Kjaer, Martin A. Fascione, Carolyn R. Bertozzi, Sabine Flitsch, Stacy A. Malaker, Ilaria Malanchi, Benjamin Schumann, Mahmoud-Reza Rafiee, Acely Garza-Garcia, Aristotelis Antonopoulos, Stuart M. Haslam
Summary: In this study, a strategy called BOCTAG was developed to label glycoproteins by equipping cells with an artificial biosynthetic pathway. The method was demonstrated to be applicable in co-culture and mouse models, allowing for the annotation of cell-specific glycosylation sites.
NATURE COMMUNICATIONS
(2022)
Article
Microbiology
Stephanie D. Nofal, Caia Dominicus, Malgorzata Broncel, Nicholas J. Katris, Helen R. Flynn, Gustavo Arrizabalaga, Cyrille Y. Botte, Brandon M. Invergo, Moritz Treeck
Summary: In the lytic cycle of Toxoplasma gondii, calcium and cyclic nucleotide signaling pathways are connected by a positive feedback loop, which is regulated by a plant-like calcium dependent kinase (CDPK3) and a cAMP-specific phosphodiesterase (PDE2). This feedback loop allows the parasite to respond faster to egress inducers.
Article
Biology
Flavia Rosianu, Simeon R. Mihaylov, Noreen Eder, Antonie Martiniuc, Suzanne Claxton, Helen R. Flynn, Shamsinar Jalal, Marie-Charlotte Domart, Lucy Collinson, Mark Skehel, Ambrosius P. Snijders, Matthias Krause, Sharon A. Tooze, Sila K. Ultanir
Summary: This study reveals the importance of NDR1/2 kinases in maintaining neuronal health by regulating endocytosis, protein homeostasis, and autophagy. The loss of NDR1/2 results in neurodegeneration, accumulation of cellular components, and impaired autophagy efficiency.
LIFE SCIENCE ALLIANCE
(2022)
Article
Biochemical Research Methods
Beatriz Calle, Edgar Gonzalez-Rodriguez, Keira E. Mahoney, Anna Cioce, Ganka Bineva-Todd, Omur Y. Tastan, Chloe Roustan, Helen Flynn, Stacy A. Malaker, Benjamin Schumann
Summary: This paper describes a method using bump-and-hole engineering to develop chemical, bioorthogonal reporters for studying the activity of the GalNAc-T family of glycosyltransferases. It allows identification of protein substrates and glycosylation sites of individual GalNAc-Ts. Despite the need for transfection of cells with engineered transferases and enzymes, this tactic complements methods in molecular biology.
Article
Multidisciplinary Sciences
Simeon R. Mihaylov, Lydia M. Castelli, Ya-Hui Lin, Aytac Gul, Nikita Soni, Christopher Hastings, Helen R. Flynn, Oana Paun, Mark J. Dickman, Ambrosius P. Snijders, Robert Goldstone, Oliver Bandmann, Tatyana A. Shelkovnikova, Heather Mortiboys, Sila K. Ultanir, Guillaume M. Hautbergue
Summary: The RS domain of PGC-1α directly interacts with RNA and the nuclear RNA export receptor NXF1, and this RNA-binding activity is required for the nuclear export of mitochondrial-related mRNAs and mitochondrial homeostasis.
NATURE COMMUNICATIONS
(2023)
Article
Engineering, Biomedical
Matthew E. H. White, Ludwig R. Sinn, D. Marc Jones, Joost de Folter, Simran Kaur Aulakh, Ziyue Wang, Helen R. Flynn, Lynn Krueger, Pinkus Tober-Lau, Vadim Demichev, Florian Kurth, Michael Muelleder, Veronique Blanchard, Christoph B. Messner, Markus Ralser
Summary: A technique named 'OxoScan-MS' allows for the large-scale quantification of glycopeptides in plasma samples. By applying this technique, the study identified differential glycosylation in COVID-19 patients compared to healthy controls in various disease-relevant plasma glycoproteins. This technique has the potential for the quantitative mapping of glycoproteomes in a large number of samples.
NATURE BIOMEDICAL ENGINEERING
(2023)