Review
Biochemistry & Molecular Biology
Aadil Javed, Mahdieh Yarmohammadi, Kemal Sami Korkmaz, Teresa Rubio-Tomas
Summary: Gastric cancer is characterized by uncontrolled growth and metastasis of gastric epithelial cells, which is predominantly in adenocarcinoma form. The regulation of gastric cell growth is influenced by key cell cycle regulators, including Cyclins and Cyclin-dependent kinases (CDKs). Dysregulation of these molecules can lead to disturbances in cell cycle dynamics and the development of gastric cancer. Numerous studies have examined the roles of Cyclins and CDKs in gastric cancer, and this review aims to compile evidence of upstream regulators that activate or inhibit Cyclins and CDKs. It serves as a comprehensive resource for future studies and hypothesis generation.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Medicine, Research & Experimental
Ting-Yu Chang, Kunal Nepali, Yi-Ying Chen, Yu-Chen S. H. Yang, Kai-Cheng Hsu, Yun Yen, Shiow-Lin Pan, Jing-Ping Liou, Sung-Bau Lee
Summary: The study identifies MPT0L184 as a novel HDAC inhibitor that can induce premature mitosis and potentially combat drug resistance in cancers.
BIOMEDICINE & PHARMACOTHERAPY
(2021)
Review
Pharmacology & Pharmacy
Oana-Maria Thoma, Markus F. Neurath, Maximilian J. Waldner
Summary: CDKs play a key role in cell cycle regulation, with aberrant expression potentially leading to cancer development. CDK inhibitors, such as CDK4/6 inhibitors, are being investigated as novel cancer therapies.
FRONTIERS IN PHARMACOLOGY
(2021)
Review
Oncology
Soudeh Ghafouri-Fard, Tayyebeh Khoshbakht, Bashdar Mahmud Hussen, Peixin Dong, Nikolaus Gassler, Mohammad Taheri, Aria Baniahmad, Nader Akbari Dilmaghani
Summary: This article summarizes the important role of Cyclin-dependent kinases (CDK) in cancer, emphasizing the significance of understanding CDK function and mechanisms for future cancer therapies targeting these kinases.
CANCER CELL INTERNATIONAL
(2022)
Article
Chemistry, Inorganic & Nuclear
Ruilin Guan, Lina Xie, Lili Wang, Ying Zhou, Yu Chen, Liangnian Ji, Hui Chao
Summary: NecroIr1 and NecroIr2, iridium(iii) complexes, induce necroptosis in cisplatin-resistant lung cancer cells by selectively accumulating in mitochondria and causing oxidative stress. Additionally, they interfere with cell cycle progression, leading to G0/G1 phase arrest. The combined effect of necroptosis induction and cell cycle arrest makes them potential antitumor agents against drug-resistant cancer cells.
INORGANIC CHEMISTRY FRONTIERS
(2021)
Article
Biochemistry & Molecular Biology
Rojapriyadharshini Gandhimathi, Dorothea Pinotsi, Mario Koehler, Jorg Mansfeld, Caroline Ashiono, Tatjana Kleele, Sumit Pawar, Ulrike Kutay
Summary: During mitotic entry, nuclear pore complexes (NPCs) disintegrate and so do the large nuclear and cytoplasmic rings formed by Y-complexes. Y-complex Nups dissociate slower than other Nups during in vitro NPC disassembly and remain associated with mitotic ER membranes. Super-resolution microscopy reveals two types of higher-order assemblies of mitotic Y-complexes: large clusters at kinetochores and small focal ER-associated structures, which refine current models of nuclear reassembly.
Review
Oncology
Mitra Zabihi, Ramin Lotfi, Amir-Mohammad Yousefi, Davood Bashash
Summary: CDKs, cyclins, and CKIs play important roles in the cell cycle regulatory machinery, and dysregulation of their expression or function can contribute to tumorigenesis. While designing CDK inhibitors to target tumor cells shows promise, the non-canonical functions of CDKs pose challenges in their application. This review aims to explore the biology of CDKs and their contribution to tumorigenesis, and discuss the pros and cons of CDK inhibition in the treatment of human cancers.
JOURNAL OF CANCER RESEARCH AND CLINICAL ONCOLOGY
(2023)
Article
Pharmacology & Pharmacy
Lei Zhang, Biwei Ye, Yunfeng Lin, Yi-Dong Li, Jing-Quan Wang, Zhuo Chen, Feng-Feng Ping, Zhe-Sheng Chen
Summary: In this study, the researchers investigated the effect of the CDK4/6 inhibitor, ribociclib, on multidrug resistance (MDR) mediated by P-glycoprotein (P-gp) in human epidermoid carcinoma cells. They found that ribociclib increased the efficacy of a P-gp substrate drug, colchicine, by down-regulating the expression of P-gp and increasing its ATPase activity. Docking studies suggested that ribociclib interacted with the drug-substrate binding site of P-gp. Additionally, ribociclib inhibited the drug efflux activity of P-gp, leading to increased intracellular accumulation of doxorubicin. These findings suggest that ribociclib may be a potential agent for combined therapy in cancers with P-gp-mediated MDR.
FRONTIERS IN PHARMACOLOGY
(2022)
Article
Physics, Multidisciplinary
Neil Robinson, Razyq Nasharuddin, Einar O. Fridjonsson, Michael L. Johns
Summary: We observe an unexpected decay-recovery behavior in the time-dependent 1H NMR relaxation times of confined water in a porous material. The combined effects of decreasing pore size and evolving interfacial chemistry rationalize our observations, leading to a transition between surface-limited and diffusion-limited relaxation regimes. This behavior highlights the necessity of considering temporally evolving surface relaxivity in the interpretation of NMR relaxation data from complex porous systems.
PHYSICAL REVIEW LETTERS
(2023)
Review
Chemistry, Medicinal
Sonal M. Manohar
Summary: This article reviews cyclin-dependent kinases as potential targets for colorectal cancer (CRC) and discusses therapeutic candidates to target CDKs.
FUTURE MEDICINAL CHEMISTRY
(2022)
Review
Pharmacology & Pharmacy
Marzena Staniszewska, Kajetan Kielbowski, Klaudia Rusinska, Estera Bakinowska, Ewa Gromowska, Andrzej Pawlik
Summary: In this review, the potential of cyclin-dependent kinases (CDK) as novel therapeutic targets in rheumatoid arthritis (RA) and psoriasis is evaluated. CDK inhibitors show promise due to their potential multidirectional effects on osteoclastogenesis, neutrophil apoptosis, and macrophage apoptosis, all of which play important roles in the development of joint destruction and inflammation in RA and psoriasis. However, further clinical trials are needed to assess the efficacy and safety of CDK-blocking therapy in these conditions.
EXPERT OPINION ON THERAPEUTIC TARGETS
(2023)
Article
Biochemistry & Molecular Biology
Julie Jacquemyn, Joyce Foroozandeh, Katlijn Vints, Jef Swerts, Patrik Verstreken, Natalia Gounko, Sandra F. Gallego, Rose Goodchild
Summary: Torsin affects lipid metabolism by regulating NEP1R1-CTDNEP1 and Lipin, influencing nuclear envelope remodeling and nuclear pore complex biogenesis. This mechanism explains some of the pleiotropic effects of Torsins.
Review
Plant Sciences
Daniel Ludke, Philipp F. W. Rohmann, Marcel Wiermer
Summary: Plant viability and responses to changing environments depend on spatial communication between the compartments separated by the nuclear envelope, involving bidirectional exchange of proteins and RNAs mediated by a sophisticated transport machinery.
FRONTIERS IN PLANT SCIENCE
(2021)
Article
Construction & Building Technology
Zhen Jiang, Guojun Cai, Guanglin Tian, Xuening Liu
Summary: This study evaluates the effect of aggregate particle size on the pore size distribution in mortars. The results show that the surface-to-volume ratio of the aggregate is the main parameter affecting the pore structure of the mortar, with a decrease in the surface-to-volume ratio leading to a richer pore structure.
CONSTRUCTION AND BUILDING MATERIALS
(2022)
Article
Biology
Pau Pascual-Garcia, Shawn C. Little, Maya Capelson
Summary: Cells are able to develop transcriptional memory after repeated exposure to external cues, and this memory can be maintained epigenetically through cell divisions with the help of a nuclear pore component called Nup98. This study used single-molecule RNA FISH to examine the dynamics of transcription in Drosophila cells upon repeated exposure to the steroid hormone ecdysone. The results showed that cells rapidly activate a low-level transcriptional response upon hormone exposure, but also slowly transition into a specialized memory state characterized by a high rate of expression. It was found that this transition between non-memory and memory states is independent of the initial activation of transcription.
Review
Cell Biology
Kazuhiro Maeshima, Sachiko Tamura, Jeffrey C. Hansen, Yuji Itoh
CURRENT OPINION IN CELL BIOLOGY
(2020)
Article
Cell Biology
Takeshi Mizuno, Kei Hirabayashi, Sae Miyazawa, Yurika Kobayashi, Kenta Shoji, Masakazu Kobayashi, Fumio Hanaoka, Naoko Imamoto, Hidetaka Torigoe
Summary: The study investigated the interaction between DNA polymerase alpha and two paralogs of mouse POT1 telomere-binding protein, revealing their roles in lagging strand synthesis. Experimental results showed that the POT1a/b-TPP1-TIN2 complex accumulated in the nucleus, interacted with DNA polymerase alpha, and participated in telomere synthesis.
Article
Biology
Yuji Itoh, Shiori Iida, Sachiko Tamura, Ryosuke Nagashima, Kentaro Shiraki, Tatsuhiko Goto, Kayo Hibino, Satoru Ide, Kazuhiro Maeshima
Summary: 1,6-hexanediol inhibits liquid droplet formation within cells and leads to hyper-condensation of chromatin, with effects that are dose-dependent. This compound also facilitates cation-dependent chromatin condensation in vitro, distinct from its activity on liquid droplets.
LIFE SCIENCE ALLIANCE
(2021)
Article
Cell Biology
Kazuhiro Maeshima, Shiori Iida, Sachiko Tamura
Summary: Genomic information is encoded on long strands of DNA, stored in nuclear chromatin. The structure of chromatin is highly influenced by the surrounding environment, forming compact and dynamic domains that affect DNA accessibility and function. New technologies and evidence have shifted our understanding of chromatin from being regular and static to more variable and dynamic.
COLD SPRING HARBOR PERSPECTIVES IN BIOLOGY
(2021)
Article
Multidisciplinary Sciences
Claire Hoencamp, Olga Dudchenko, Ahmed M. O. Elbatsh, Sumitabha Brahmachari, Jonne A. Raaijmakers, Tom van Schaik, Angela Sedeno Cacciatore, Vinicius G. Contessoto, Roy G. H. P. van Heesbeen, Bram van den Broek, Aditya N. Mhaskar, Hans Teunissen, Brian Glenn St Hilaire, David Weisz, Arina D. Omer, Melanie Pham, Zane Colaric, Zhenzhen Yang, Suhas S. P. Rao, Namita Mitra, Christopher Lui, Weijie Yao, Ruqayya Khan, Leonid L. Moroz, Andrea Kohn, Judy St Leger, Alexandria Mena, Karen Holcroft, Maria Cristina Gambetta, Fabian Lim, Emma Farley, Nils Stein, Alexander Haddad, Daniel Chauss, Ayse Sena Mutlu, Meng C. Wang, Neil D. Young, Evin Hildebrandt, Hans H. Cheng, Christopher J. Knight, Theresa L. U. Burnham, Kevin A. Hovel, Andrew J. Beel, Pierre-Jean Mattei, Roger D. Kornberg, Wesley C. Warren, Gregory Cary, Jose Luis Gomez-Skarmeta, Veronica Hinman, Kerstin Lindblad-Toh, Federica Di Palma, Kazuhiro Maeshima, Asha S. Multani, Sen Pathak, Liesl Nel-Themaat, Richard R. Behringer, Parwinder Kaur, Rene H. Medema, Bas van Steensel, Elzo de Wit, Jose N. Onuchic, Michele Di Pierro, Erez Lieberman Aiden, Benjamin D. Rowland
Summary: The study identified two types of three-dimensional genome architectures at the chromosome scale in eukaryotes, with one type correlated with the absence of condensin II subunits. Depletion of condensin II in humans results in a genome structure resembling that of fungi or mosquitoes. The research proposes a physical model in which condensin II compacts chromosomes lengthwise during mitosis, influencing the chromosome-scale genome architecture.
Article
Cell Biology
Philip Gunkel, Haruki Iino, Sandra Krull, Volker C. Cordes
Summary: The nuclear basket (NB) scaffold is a fibrillar structure composed of coiled-coil dominated protein TPR, to which other proteins can bind without affecting structural integrity. The discovery of vertebrate protein ZC3HC1 as a new component of the NB expands its functional repertoire, affecting different types of cell nuclear envelopes (NE). This suggests a more complex NB structure than previously thought.
Article
Biochemistry & Molecular Biology
Yuji Itoh, Esmae J. Woods, Katsuhiko Minami, Kazuhiro Maeshima, Rosana Collepardo-Guevara
Summary: Chromatin in eukaryotic cells is a complex structure comprised of DNA, histones, and associated proteins, exhibiting dynamic liquid-like behavior and undergoing structural variations within the cell. Advanced imaging techniques have allowed for the observation of these characteristics, while computational modeling has provided insight into the molecular mechanisms behind this behavior, highlighting the importance of chromatin dynamics in living cells.
CURRENT OPINION IN STRUCTURAL BIOLOGY
(2021)
Article
Genetics & Heredity
Satoru Ide, Asuka Sasaki, Yusuke Kawamoto, Toshikazu Bando, Hiroshi Sugiyama, Kazuhiro Maeshima
Summary: The new PI-PRICh method allows effective isolation of specific chromatin segments and identification of both protein and RNA components. This approach shows good reproducibility in identifying telomeric chromatin, providing a promising alternative for studying chromatin organization and functions within the cell.
EPIGENETICS & CHROMATIN
(2021)
Article
Biology
Shingo Kose, Kenichiro Imai, Ai Watanabe, Akira Nakai, Yutaka Suzuki, Naoko Imamoto
Summary: Hikeshi mediates the nuclear import of HSP70 and regulates its nucleocytoplasmic distribution and functions. Nuclear HSP70 affects the transcriptional activity of HSF1 and nuclear proteostasis. Depletion of Hikeshi leads to reduced nuclear HSP70 levels and up-regulation of HSF1-regulated gene expression.
LIFE SCIENCE ALLIANCE
(2022)
Article
Biochemistry & Molecular Biology
Satoru Ide, Sachiko Tamura, Kazuhiro Maeshima
Summary: The chromatin, consisting of nucleosomes and associated proteins and RNAs, plays a critical role in regulating genome functions. Single-nucleosome imaging is an effective method to investigate the behavior of chromatin in living cells, providing insights into its organization and dynamics not observed in fixed cells. Analyzing the motion data from various aspects can contribute to a better understanding of genome functions.
Editorial Material
Multidisciplinary Sciences
Kazuhiro Maeshima
Article
Multidisciplinary Sciences
Shiori Iida, Soya Shinkai, Yuji Itoh, Sachiko Tamura, Masato T. Kanemaki, Shuichi Onami, Kazuhiro Maeshima
Summary: The study revealed that local chromatin motion remains steady in live human cells throughout the phases of G1, S, and G2, driven mainly by thermal fluctuations, with an increase in motion following a DNA damage response. These findings support the viscoelastic properties of chromatin and suggest that steady-state chromatin motion enables cells to perform housekeeping functions during interphase.
Editorial Material
Cell Biology
Kazuhiro Maeshima, Eran Meshorer
CURRENT OPINION IN CELL BIOLOGY
(2022)
Article
Cell Biology
Philip Gunkel, Haruki Iino, Sandra Krull, Volker C. Cordes
Summary: Proteins ZC3HC1 and TPR are key components of the nuclear basket, which is attached to the nucleoplasmic side of the nuclear pore complex. ZC3HC1 initially binds to the nuclear basket in a TPR-dependent manner and can recruit additional TPR polypeptides to this structure.
MOLECULAR BIOLOGY OF THE CELL
(2023)
Article
Multidisciplinary Sciences
Tadasu Nozaki, Soya Shinkai, Satoru Ide, Koichi Higashi, Sachiko Tamura, Masa A. Shimazoe, Masaki Nakagawa, Yutaka Suzuki, Yasushi Okada, Masaki Sasai, Shuichi Onami, Ken Kurokawa, Shiori Iida, Kazuhiro Maeshima
Summary: In eukaryotes, the physical nature of higher-order chromatin organization in living cells, such as whether it is condensed or extended and whether it is liquid-like or solid-like, remains unclear. In this study, novel approaches combining genomics, single-nucleosome imaging, and computational modeling were used to investigate the physical organization and behavior of early DNA replicated regions in human cells. The results showed that nucleosomes form physically condensed domains with approximately 150-nm diameters, even in active chromatin regions. The behavior of nucleosomes within these domains is liquid-like on the scale of 150 nm/0.5 s, facilitating chromatin accessibility, while at larger scales, chromatin behaves more like a solid, potentially contributing to genome integrity.