Article
Biology
Xiaoxue Zhou, Wenxue Li, Yansheng Liu, Angelika Amon
Summary: The mitotic exit network (MEN) in budding yeast integrates spatial and temporal cues to promote exit from mitosis by transmitting signals and kinase complex localization from the cytoplasmic face of spindle pole bodies (SPBs) to the nucleolus where the MEN effector protein Cdc14 resides.
Article
Biochemistry & Molecular Biology
Carolina Villarroya-Beltri, Ana Filipa B. Martins, Alejandro Garcia, Daniel Gimenez, Eduardo Zarzuela, Monica Novo, Cristina Del Alamo, Jose Gonzalez-Martinez, Gloria C. Bonel-Perez, Irene Diaz, Maria Guillamot, Massimo Chiesa, Ana Losada, Osvaldo Grana-Castro, Meritxell Rovira, Javier Munoz, Maria Salazar-Roa, Marcos Malumbres
Summary: Maintenance of stemness is regulated by CDC14, a CDK-counteracting phosphatase, which dephosphorylates UTF1 to trigger its degradation and control neural differentiation. Lack of CDC14 results in deficient neural system development and impaired neural differentiation from ESCs. CDC14 phosphatases are critical molecular switches linking cell cycle regulation and self-renewal.
Article
Multidisciplinary Sciences
Patrick Partscht, Alexander Simon, Nan-Peng Chen, Sylvia Erhardt, Elmar Schiebel
Summary: Mitotic perturbations activate the spindle assembly checkpoint (SAC), causing cells to stay in prometaphase with high CDK1 activity. Prolonged mitotic arrest is bypassed by gradual cyclin B decline followed by slip-page of cells into G1 without chromosome segregation. HIPK2 kinase accumulates in mitotic cells and phosphorylates the Rett syndrome protein MeCP2 at Ser92, leading to enhanced translation of cyclin B1, which helps counteract the proteolytic decline of cyclin B1 and suspend mitotic slip-page. The HIPK2/CDC14B-MeCP2 axis functions as an enhancer of the SAC-induced mitotic block.
Article
Cell Biology
Gabriel M. Gihana, Arthur A. Cross-Najafi, Soni Lacefield
Summary: In budding yeast, the Cdc42 GTPase establishes a polar front during G1, with the activity of the Cdc14 phosphatase released through the mitotic exit network playing a crucial role in redistributing Cdc42 between mother and daughter cells. The interaction between Bem3, a Cdc42 GAP, and Cdc14 is important for the dephosphorylation and activation of Bem3, allowing for the inactivation and redistribution of Cdc42. These findings reveal a mechanism by which Cdc14 regulates the spatial and temporal activity of Cdc42 to maintain normal cell size at cytokinesis.
JOURNAL OF CELL BIOLOGY
(2021)
Review
Biochemistry & Molecular Biology
Patrick Partscht, Elmar Schiebel
Summary: CDC14 was initially identified as a crucial mediator of mitotic exit in budding yeast, belonging to the family of dual-specificity phosphatases (DUSPs) that are present in most eukaryotes. Contradicting data regarding the conservation of a cell cycle role in human paralogs CDC14A and CDC14B have sparked a contentious discussion, but redundancy may mask this role. Subsequent studies on CDC14A and CDC14B double knockouts in human and mouse have demonstrated that CDC14 activity is dispensable for mitotic progression in higher eukaryotes and instead suggested functional specialization.
Article
Biochemistry & Molecular Biology
Josh Lawrimore, Daniel Kolbin, John Stanton, Muznah Khan, Solenn C. de Larminat, Colleen Lawrimore, Elaine Yeh, Kerry Bloom
Summary: The nucleolus is the site of ribosome biosynthesis, where the rDNA locus and Cdc14 protein behave like a condensate formed by polymer-polymer phase separation, while ribonucleoproteins behave like a condensate formed by liquid-liquid phase separation. The compaction and distribution in the nucleolus are dependent on the concentration of DNA cross-linkers.
NUCLEIC ACIDS RESEARCH
(2021)
Article
Biochemistry & Molecular Biology
Yumi Ueki, Michael A. Hadders, Melanie B. Weisser, Isha Nasa, Paula Sotelo-Parrilla, Lauren E. Cressey, Tanmay Gupta, Emil P. T. Hertz, Thomas Kruse, Guillermo Montoya, A. Arockia Jeyaprakash, Arminja Kettenbach, Susanne M. A. Lens, Jakob Nilsson
Summary: The study reveals the structure and function of the PP2A-B56-hSgo1 complex during mitosis, highlighting the essential role of a conserved pocket on the B56 regulatory subunit for hSgo1 binding and cohesion protection. Additionally, it shows that hSgo1 inhibits the binding of PP2A-B56 substrates and that PP2A-B56 dephosphorylates Cdk1 sites on hSgo1 to regulate cohesin interactions. Overall, the research provides important insights into cohesion protection during mitosis.
Review
Cell Biology
Vincent Archambault, Jingjing Li, Virginie Emond-Fraser, Myreille Larouche
Summary: In most animal cell types, the disassembly of the interphase nucleus during mitotic entry is well-studied, but the mechanisms of nuclear reassembly at the end of mitosis are less understood. Recent research has made progress in deciphering the roles of dephosphorylation events in promoting nuclear envelope reassembly, chromosome decondensation, kinetochore disassembly, and interphase chromatin organization. The precise roles and regulation of protein phosphatases in this process, particularly the PP1 and PP2A groups, are being elucidated.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Helena Maria Schnell, Marco Jochem, Yagmur Micoogullari, Claire Louise Riggs, Pavel Ivanov, Hendrik Welsch, Rini Ravindran, Paul Anderson, Lucy Christina Robinson, Kelly Tatchell, John Hanna
Summary: Cellular function is mainly differentiated through membrane-bound organelles, but recent research has shown that membraneless structures formed through phase separation can also achieve compartmentalization in liquid droplet-like properties. Arsenite-induced cytoplasmic stress granules play a significant role in protein homeostasis by regulating translation, with the catalytic subunit Glc7 of protein phosphatase-1 being involved in their formation. This stress-induced granule is highly specific to arsenite and controls translation through a new mode of translational control by Glc7, independently of its established role in regulating eIF2 alpha.
Article
Biochemistry & Molecular Biology
Marcel Albacar, Diego Velazquez, Antonio Casamayor, Joaquin Arino
Summary: Overexpression of protein phosphatase Ppz1 in Saccharomyces cerevisiae strongly inhibits cell growth. However, overexpression of its subunit Hal3 can completely counteract the toxic effects caused by excess Ppz1. Hal3 not only inhibits the enzymatic activity of Ppz1, but also recruits the phosphatase to internal structures.
Article
Biochemistry & Molecular Biology
Jamin B. Hein, Hieu T. Nguyen, Dimitriya H. Garvanska, Isha Nasa, Thomas Kruse, Yinnian Feng, Blanca Lopez Mendez, Norman Davey, Arminja N. Kettenbach, Polly M. Fordyce, Jakob Nilsson
Summary: Investigating the specificity of phosphoprotein phosphatases (PPPs) has been challenging, but this study introduces a novel approach, MRBLE:Dephos, to determine phosphatase preferences. Using this method, the authors identified amino acid preferences of residues surrounding the dephosphorylation site for PP1 and PP2A-B55, and discovered key dephosphorylation sites during mitotic exit that are consistent with MRBLE:Dephos results.
MOLECULAR SYSTEMS BIOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Florentin Huguet, Ezgi Gokan, Helen A. A. Foster, Hasnat A. A. Amin, Paola Vagnarelli
Summary: Lamin A phosphorylation and de-phosphorylation are important regulatory mechanisms during cell division, which are involved in nuclear envelope disassembly and reformation, as well as gene expression regulation. Repo-Man/PP1 phosphatase mediates the de-phosphorylation of Lamin A S22, and their interaction is mediated by SUMOylation.
Article
Cell Biology
Takanobu Moriuchi, Fumiko Hirose
Summary: RepoMan, a regulatory subunit of protein phosphatase 1 (PP1), is transiently modified with SUMO-2 during late telophase, which enhances its binding affinity with lamin A and contributes to the recruitment and dephosphorylation of lamin A. Transient SUMOylation of RepoMan plays a crucial role in the spatiotemporal regulation of lamin A dephosphorylation and subsequent nuclear lamina formation at the end of mitosis.
JOURNAL OF CELL SCIENCE
(2021)
Article
Multidisciplinary Sciences
Chihiro Yamada, Aya Morooka, Seira Miyazaki, Masayoshi Nagai, Satoru Mase, Kenji Iemura, Most Naoshia Tasnin, Tsuneyuki Takuma, Shotaro Nakamura, Shamsul Morshed, Naoki Koike, Md Golam Mostofa, Muhammad Arifur Rahman, Tasnuva Sharmin, Haruko Katsuta, Kotaro Ohara, Kozo Tanaka, Takashi Ushimaru
Summary: This study reveals that the inactivation of TORC1 kinase triggers mitotic slippage in yeast and human cells, leading to chromosome instability. However, the mechanism of mitotic slippage differs between yeast and human cells. This unexpected involvement of TORC1 in mitosis highlights the potential undesirable side effects of TORC1 inhibitors as immunosuppressants and anti-tumor drugs.
Article
Cell Biology
York Posor, Charis Kampyli, Benoit Bilanges, Sushila Ganguli, Philipp A. Koch, Alexander Wallroth, Daniele Morelli, Michalina Jenkins, Samira Alliouachene, Elitza Deltcheva, Buzz Baum, Volker Haucke, Bart Vanhaesebroeck
Summary: This study uncovers a pathway by which the phosphoinositide lipid switch, phosphatidylinositol-3,4-bisphosphate (PtdIns(3,4)P2), promotes the disassembly of focal adhesions through regulating the activity of RhoA-dependent stress fibers.
DEVELOPMENTAL CELL
(2022)
Article
Chemistry, Medicinal
Celeste Alverez, Stacie L. Bulfer, Ramappa Chakrasali, Michael S. Chimenti, Raymond J. Deshaies, Neal Green, Mark Kelly, Matthew G. LaPorte, Taber S. Lewis, Mary Liang, William J. Moore, R. Jeffrey Neitz, Vsevolod A. Peshkov, Michael A. Walters, Feng Zhang, Michelle R. Arkin, Peter Wipf, Donna M. Huryn
ACS MEDICINAL CHEMISTRY LETTERS
(2016)
Editorial Material
Biochemistry & Molecular Biology
Gary Kleiger, Raymond Deshaies
Letter
Biochemistry & Molecular Biology
Janakiram R. Vangala, Franziska Sotzny, Elke Krueger, Raymond J. Deshaies, Senthil K. Radhakrishnan
Article
Biochemistry & Molecular Biology
Veronika Reiterer, Cristina Figueras-Puig, Francois Le Guerroue, Stefano Confalonieri, Manuela Vecchi, Dasaradha Jalapothu, Sandip M. Kanse, Raymond J. Deshaies, Pier Paolo Di Fiore, Christian Behrends, Hesso Farhan
Article
Biochemical Research Methods
Liang Xue, Emily E. Blythe, Elyse C. Freiberger, Jennifer L. Mamrosh, Alexander S. Hebert, Justin M. Reitsma, Sonja Hess, Joshua J. Coon, Raymond J. Deshaies
MOLECULAR & CELLULAR PROTEOMICS
(2016)
Article
Cell Biology
Min-Kyung Sung, Justin M. Reitsma, Michael J. Sweredoski, Sonja Hess, Raymond J. Deshaies
MOLECULAR BIOLOGY OF THE CELL
(2016)
Article
Biochemistry & Molecular Biology
T. Van Nguyen, J. Eugene Lee, Michael J. Sweredoski, Seung-Joo Yang, Seung-Je Jeon, Joseph S. Harrison, Jung-Hyuk Yim, Sang Ghil Lee, Hiroshi Handa, Brian Kuhlman, Ji-Seon Jeong, Justin M. Reitsma, Chul-Seung Park, Sonja Hess, Raymond J. Deshaies
Article
Biology
Min-Kyung Sung, Tanya R. Porras-Yakushi, Justin M. Reitsma, Ferdinand M. Huber, Michael J. Sweredoski, Andre Hoelz, Sonja Hesse, Raymond J. Deshaies
Article
Chemistry, Medicinal
Christian Perez, Jing Li, Francesco Parlati, Matthieu Rouffett, Yuyong Ma, Andrew L. Mackinnon, Tsui-Fen Chou, Raymond J. Deshaies, Seth M. Cohen
JOURNAL OF MEDICINAL CHEMISTRY
(2017)
Article
Biochemistry & Molecular Biology
Jing Li, Tanya Yakushi, Francesco Parlati, Andrew L. Mackinnon, Christian Perez, Yuyong Ma, Kyle P. Carter, Sharon Colayco, Gavin Magnuson, Brock Brown, Kevin Nguyen, Stefan Vasile, Eigo Suyama, Layton H. Smith, Eduard Sergienko, Anthony B. Pinkerton, Thomas D. Y. Chung, Amy E. Palmer, Ian Pass, Sonja Hess, Seth M. Cohen, Raymond J. Deshaies
NATURE CHEMICAL BIOLOGY
(2017)
Article
Biochemistry & Molecular Biology
Linda Lauinger, Jing Li, Anton Shostak, Ibrahim Avi Cemel, Nati Ha, Yaru Zhang, Philipp E. Merkl, Simon Obermeyer, Nicolas Stankovic-Valentin, Tobias Schafmeier, Walter J. Wever, Albert A. Bowers, Kyle P. Carter, Amy E. Palmer, Herbert Tschochner, Frauke Melchior, Raymond J. Deshaies, Michael Brunner, Axel Diernfellner
NATURE CHEMICAL BIOLOGY
(2017)
Article
Multidisciplinary Sciences
Thang Van Nguyen, Jing Li, Chin-Chun (Jean) Lu, Jennifer L. Mamrosh, Gang Lu, Brian E. Cathers, Raymond J. Deshaies
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2017)
Article
Biochemistry & Molecular Biology
Mark A. Nakasone, Timothy A. Lewis, Olivier Walker, Anita Thakur, Wissam Mansour, Carlos A. Castaneda, Jennifer L. Goeckeler-Fried, Frank Parlati, Tsui-Fen Chou, Ortal Hayat, Daoning Zhang, Christina M. Camara, Steven M. Bonn, Urszula K. Nowicka, Susan Krueger, Michael H. Glickman, Jeffrey L. Brodsky, Raymond J. Deshaies, David Fushman
Review
Multidisciplinary Sciences
Raymond J. Deshaies
Article
Biochemistry & Molecular Biology
Justin M. Reitsma, Xing Liu, Kurt M. Reichermeier, Annie Moradian, Michael J. Sweredoski, Sonja Hess, Raymond J. Deshaies