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Biochemistry & Molecular Biology
Lucie Knoblochova, Tomas Duricek, Michaela Vaskovicova, Chrysoula Zorzompokou, Diana Rayova, Ivana Ferencova, Vladimir Baran, Richard M. Schultz, Eva R. Hoffmann, David Drutovic
Summary: Checkpoint kinase CHK1 regulates cell cycle progression in early mouse embryos by restraining CDK1 kinase activity through CDC25A phosphatase degradation. It also ensures the long G2 phase needed for genome activation and reprogramming gene expression in two-cell stage mouse embryos. Depletion of CHK1 leads to DNA damage and chromosome segregation errors, resulting in aneuploidy and infertility.
Article
Biochemistry & Molecular Biology
Lau Yan Ng, Hoi Tang Ma, Randy Y. C. Poon
Summary: In this study, an inverse relationship between cyclin A and CDC25A, two CDK activators, was uncovered. Destruction of cyclin A promoted an acute accumulation of CDC25A, mainly through transcriptional upregulation rather than protein stability changes. This compensatory mechanism involving CDC25A ensures timely mitotic entry at different levels of cyclin A deficiency.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2023)
Article
Biochemistry & Molecular Biology
Pim J. Huis in 't Veld, Sabine Wohlgemuth, Carolin Koerner, Franziska Muller, Petra Janning, Andrea Musacchio
Summary: During cell division into mitosis, CDK1 and Cyclin-B complex phosphorylate proteins, altering their conformations and functions; to study the mitotic protein machinery, a pure and active kinase complex must be reconstituted in vitro; high activity of CDK1:Cyclin-B complex can be achieved through the activation of a Threonine residue in the CDK1 activation loop.
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Cell Biology
Lisa Donker, Ronja Houtekamer, Marjolein Vliem, Francois Sipieter, Helena Canever, Manuel Gomez-Gonzalez, Miquel Bosch-Padros, Willem-Jan Pannekoek, Xavier Trepat, Nicolas Borghi, Martijn Gloerich
Summary: Epithelial cells adapt their rate of cell division by sensing changes in cell number through mechanosensitive E-cadherin adhesions, which control G2/M cell-cycle progression.
Review
Biochemistry & Molecular Biology
Jorrit M. Enserink, Pierre Chymkowitch
Summary: Cdk1 is a master regulator of the cell cycle, controlling progression through different phases. It also directly regulates RNA polymerase activity, which is important for protein synthesis and meeting cellular demands. This regulation promotes cell cycle entry.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Biochemistry & Molecular Biology
Martina Barbiero, Luca Cirillo, Sapthaswaran Veerapathiran, Catherine Coates, Camilla Ruffilli, Jonathon Pines
Summary: This study uses fluorescence correlation spectroscopy and fluorescence cross-correlation spectroscopy to investigate the dynamics of the cell cycle machinery. The results show the existence of an unbound pool of Cyclin B1 in living cells and demonstrate that the affinity of Cyclin B1 for Cdk1 increases during the cell cycle, indicating regulated assembly of the complex.
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Oncology
Shigeo Ohba, Yongjian Tang, Tor-Christian Aase Johannessen, Joydeep Mukherjee
Summary: PKM2 interacts with and enhances the activation of the Cdk1-cyclin B complex, thereby directly controlling the progression of mitosis and the growth of brain tumor cells.
FRONTIERS IN ONCOLOGY
(2022)
Article
Developmental Biology
Jiahui Du, Junjun Jing, Shuo Chen, Yuan Yuan, Jifan Feng, Thach-Vu Ho, Prerna Sehgal, Jian Xu, Xinquan Jiang, Yang Chai
Summary: The research reveals that Arid1a maintains tissue homeostasis by inhibiting the Aurka-Cdk1 axis, limiting proliferation of TACs, and promoting their differentiation, while loss of Arid1a leads to reduction of the MSC population.
Article
Biochemistry & Molecular Biology
Jason M. Keaton, Benjamin G. Workman, Linfeng Xie, James R. Paulson
Summary: We demonstrate that specific inactivation of the protein kinase Cdk1/cyclin B triggers exit from mitosis in budding yeast, and that inactivation of Cdk1 is both necessary and sufficient to initiate the transition from mitosis to G1 phase. Using this system, we show that protein phosphatase 1 is required for mitotic exit and reestablishment of interphase following Cdk1 inactivation, and propose the use of this system to test the requirement of other protein phosphatases.
CHROMOSOME RESEARCH
(2023)
Article
Cell Biology
Jennifer P. Ditano, Nandini Sakurikar, Alan Eastman
Summary: CDK complexes play crucial roles in cell cycle regulation, with CDK2 being regulated by different cyclin partners. Changes in phosphorylation status of CDC25A affect CDK2 activity. Inhibition of CHK1 results in accumulation of CDC25A and activation of CDK2.
Article
Biochemistry & Molecular Biology
Siobhan O'Brien, Susan Kelso, Zachary Steinhart, Stephen Orlicky, Monika Mis, Yunhye Kim, Sichun Lin, Frank Sicheri, Stephane Angers
Summary: This study reports a novel synthetic lethal genetic interaction between FBXW7 and CCNL1 and identifies CCNL1 as a substrate of the SCF-FBXW7 E3 ligase. Defective CCNL1 accumulation resulting from FBXW7 mutation leads to shorter mitotic time. Cells with FBXW7 loss-of-function mutations are highly sensitive to treatment with a CDK11 inhibitor, suggesting a potential genetic vulnerability for cancer treatment.
Article
Biochemistry & Molecular Biology
Ilona Faustova, Kaidi Moll, Ervin Valk, Mart Loog, Mihkel Ord
Summary: Cyclins not only activate CDK complexes, but also serve as docking scaffolds for CDK substrates and inhibitors. G1-cyclins in yeast play a specific role in promoting bud growth and polarization, essential for cell survival. The discovery of a specific docking motif in G1-cyclins expands our understanding of cyclin specificity mechanisms.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Biochemistry & Molecular Biology
Antonio Galarreta, Pablo Valledor, Patricia Ubieto-Capella, Vanesa Lafarga, Eduardo Zarzuela, Javier Munoz, Marcos Malumbres, Emilio Lecona, Oscar Fernandez-Capetillo
Summary: Inhibitors of USP7 lead to widespread activation of CDK1 throughout the cell cycle, causing DNA damage and toxicity to mammalian cells. Additionally, USP7 interacts with the phosphatase PP2A, facilitating its active localization in the cytoplasm, and inhibition of USP7 or PP2A results in similar changes in the phosphoproteome, including increased phosphorylation of CDK1 targets.
Article
Cell Biology
Chenxi Zhou, Hayden A. Homer
Summary: During fertilization in mice, Cdk1 activity, cell division, and pronuclear formation go through two pauses, with the first pause triggering cell division and the second pause triggering pronuclear formation. Both pauses require the inhibitory Cdk1 kinase Wee1B, but only the first pause involves the degradation of cyclin B1.
Article
Cell Biology
Aymen al-Rawi, Edward Kaye, Svitlana Korolchuk, Jane A. Endicott, Tony Ly
Summary: Ordered protein phosphorylation by CDKs is a key mechanism for regulating the cell cycle. We show how CDK1 activity and non-catalytic CDK1 subunits contribute to the choice of substrate and site of phosphorylation using a fixed cell kinase assay and phosphoproteomics. Contrary to the model of CDK1 as an exclusively proline-directed kinase, Cyclin A and Cks1 enhance non-proline-directed phosphorylation, preferably on sites with a +3 lysine residue.
Article
Multidisciplinary Sciences
Fotini Vogiatzi, Dominique T. Brandt, Jean Schneikert, Jeannette Fuchs, Katharina Grikscheit, Michael Wanzel, Evangelos Pavlakis, Jol P. Charles, Oleg Timofeev, Andrea Nist, Marco Mernberger, Eva J. Kantelhardt, Udo Siebolts, Frank Bartel, Ralf Jacob, Ariane Rath, Roland Moll, Robert Grosse, Thorsten Stiewe
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2016)
Article
Biology
Onur Cizmecioglu, Jing Ni, Shaozhen Xie, Jean J. Zhao, Thomas M. Roberts
Article
Cell Biology
Onur Cizmecioglu, Annekatrin Krause, Ramona Bahtz, Lena Ehret, Nisar Malek, Ingrid Hoffmann
JOURNAL OF CELL SCIENCE
(2012)
Article
Biochemistry & Molecular Biology
A. T. Pores Fernando, S. Andrabi, O. Cizmecioglu, C. Zhu, D. M. Livingston, J. M. G. Higgins, B. S. Schaffhausen, T. M. Roberts
Article
Multidisciplinary Sciences
Indra Tumurbaatar, Onur Cizmecioglu, Ingrid Hoffmann, Ingrid Grummt, Renate Voit
Article
Multidisciplinary Sciences
Joel P. Charles, Jeannette Fuchs, Mirjam Hefter, Jonas B. Vischedyk, Maximilian Kleint, Fotini Vogiatzi, Jonas A. Schaefer, Andrea Nist, Oleg Timofeev, Michael Wanzel, Thorsten Stiewe
NATURE COMMUNICATIONS
(2014)
Article
Cell Biology
Oleg Timofeev, Katharina Schlereth, Michael Wanzel, Attila Braun, Bernhard Nieswandt, Axel Pagenstecher, Andreas Rosenwald, Hans-Peter Elsaesser, Thorsten Stiewe
Article
Biochemistry & Molecular Biology
Oleg Timofeev, Boris Klimovich, Jean Schneikert, Michael Wanzel, Evangelos Pavlakis, Julia Noll, Samet Mutlu, Sabrina Elmshaeuser, Andrea Nist, Marco Mernberger, Boris Lamp, Ulrich Wenig, Alexander Brobeil, Stefan Gattenloehner, Kernt Koehler, Thorsten Stiewe
Article
Cell Biology
Boris Klimovich, Thorsten Stiewe, Oleg Timofeev
Article
Multidisciplinary Sciences
Boris Klimovich, Samet Mutlu, Jean Schneikert, Sabrina Elmshaeuser, Maria Klimovich, Andrea Nist, Marco Mernberger, Oleg Timofeev, Thorsten Stiewe
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2019)
Article
Oncology
Oleg Timofeev, Lukas Koch, Constantin Niederau, Alina Tscherne, Jean Schneikert, Maria Klimovich, Sabrina Elmshaeuser, Marie Zeitlinger, Marco Mernberger, Andrea Nist, Christian Osterburg, Volker Doetsch, Martin Hrabe de Angelis, Thorsten Stiewe
Article
Multidisciplinary Sciences
Niklas Gremke, Pierfrancesco Polo, Aaron Dort, Jean Schneikert, Sabrina Elmshauser, Corinna Brehm, Ursula Klingmuller, Anna Schmitt, Hans Christian Reinhardt, Oleg Timofeev, Michael Wanzel, Thorsten Stiewe
NATURE COMMUNICATIONS
(2020)
Review
Oncology
Oleg Timofeev, Thorsten Stiewe
Summary: p53 is a DNA-binding protein that activates genes to suppress cancer cells, and its mutations, including cooperativity mutations, can lead to tumorigenesis. Understanding the structural basis of p53's DNA binding cooperativity is important for cancer therapy, as it plays a critical role in controlling cell fate decisions and tumor suppression. Research on p53 has provided insights into its function and potential personalized treatments for cancer patients with cooperativity mutations.
Article
Biochemistry & Molecular Biology
Boris Klimovich, Nastasja Merle, Michelle Neumann, Sabrina Elmshaeuser, Andrea Nist, Marco Mernberger, Daniel Kazdal, Albrecht Stenzinger, Oleg Timofeev, Thorsten Stiewe
Summary: Partial loss-of-function mutations of p53 play a significant role in tumorigenesis, leading to mutant p53 protein accumulation similar to hotspot mutations. Unlike p53 loss, these mutations enhance apoptotic chemotherapy response and improve survival rates in a therapy context.
Article
Oncology
Oleg Timofeev, Thorsten Stiewe
MOLECULAR & CELLULAR ONCOLOGY
(2017)