Article
Biochemistry & Molecular Biology
Heriati Sitosari, Ikkei Morimoto, Yao Weng, Yilin Zheng, Yoko Fukuhara, Mika Ikegame, Hirohiko Okamura
Summary: Post-translational modification (PTM) is crucial for biological events, such as bone metabolism modulation. Phosphorylation and O-GlcNAcylation can occur at the same site in proteins and may cause crosstalk between molecules. PP2A plays a major role in dephosphorylation, while OGT mediates O-GlcNAc modifications. PP2A inhibition affects OGT localization and expression, as shown in osteoblastic MC3T3-E1 cells treated with OA. The change in OGT localization is due to increased mitochondrial OGT expression and translocation of the nucleocytoplasmic isoform. Knockdown of PP2A Ca significantly affects OGT expression, indicating an interaction between PP2A and OGT that strengthens the concept of phosphorylation-O-GlcNAcylation interaction.
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
(2023)
Review
Biochemistry & Molecular Biology
Rahul S. Patil, Anita Kovacs-Kasa, Boris A. Gorshkov, David J. R. Fulton, Yunchao Su, Robert K. Batori, Alexander D. Verin
Summary: Vascular barrier dysfunction, characterized by increased permeability and inflammation of endothelial cells, plays a crucial role in acute lung injury, ARDS, sepsis, and COVID-19. Ser/Thr protein phosphatases (PPases), including PP1 and PP2A, are important regulators of endothelial barrier integrity and cytoskeletal remodeling. Understanding the role of PPases in EC barrier regulation can provide insights into the development of therapeutic strategies for these lung diseases.
Article
Plant Sciences
Xunlu Zhu, Guoxin Shen, Inosha Wijewardene, Yifan Cai, Nardana Esmaeili, Li Sun, Hong Zhang
Summary: Ethylene is a key plant hormone that regulates growth, development, and defense responses. The study demonstrates that PP2A-B'zeta positively regulates plant germination and seedling development, while also negatively regulating ethylene signaling pathway through interaction with CTR1. Further research is needed to fully understand the role of PP2A in ethylene responses.
PLANT PHYSIOLOGY AND BIOCHEMISTRY
(2021)
Article
Biology
Anna Aakula, Mukund Sharma, Francesco Tabaro, Reetta Natkin, Jesse Kamila, Henrik Honkanen, Matthieu Schapira, Cheryl Arrowsmith, Matti Nykter, Jukka Westermarck
Summary: RAS-mediated human cell transformation requires inhibition of PP2A, and the co-regulated phosphosites on proteins involved in epigenetic gene regulation were discovered in this study. RAS and PP2A co-regulate phosphorylation sites on HDAC1/2, KDM1A, MTA1/2, RNF168, and TP53BP1. The study validates the regulation of HDAC1/2 chromatin recruitment, RNF168-TP53BP1 interaction, and gene expression by RAS and PP2A. This work provides insights into the convergence of RAS and PP2A in cancer.
LIFE SCIENCE ALLIANCE
(2023)
Article
Biochemistry & Molecular Biology
Shaolong Zhang, Jingping Zhou, Pengzhao Shang, Guomeng Zhao, Anlei Wang, Jinlei Mao, Yuhang Tao, Ziyi Chen, Xuehao Wang, Changying Guo
Summary: The study reveals that genetic deletion of SE translocation (SET) inhibits the infiltration of tumor-associated macrophages (TAMs) into hypoxic tumor regions, thereby suppressing their proangiogenic and immunosuppressive functions and ultimately inhibiting tumor growth.
EXPERIMENTAL AND MOLECULAR MEDICINE
(2022)
Article
Cell Biology
Luca Orlando, Borko Tanasijevic, Mio Nakanishi, Jennifer C. Reid, Juan L. Garcia-Rodriguez, Kapil Dev Chauhan, Deanna P. Porras, Lili Aslostovar, Justin D. Lu, Zoya Shapovalova, Ryan R. Mitchell, Allison L. Boyd, Mickie Bhatia
Summary: Phosphorylation state of HV H2A.X regulates self-renewal and differentiation of human pluripotent stem cells and leukemic progenitors, with potential implications for somatic cancer stem cell control by targeting specific genomic loci.
Article
Biochemistry & Molecular Biology
Sana Ando, Masashi Sakurai, Shusaku Shibutani, Nobuyuki Kimura, Nobuhiro Shimozawa, Yasuhiro Yasutomi, Ryotaro Yabe, Takashi Ohama, Koichi Sato
Summary: The study found that brain aging in cynomolgus monkeys is closely related to changes in PP2A methylation. As monkeys age, the activity of PP2A decreases and its methylation level also decreases.
JOURNAL OF BIOCHEMISTRY
(2023)
Article
Biochemistry & Molecular Biology
Vanessa Gerlt, Juliane Mayr, Juliana Del Sarto, Stephan Ludwig, Yvonne Boergeling
Summary: The study demonstrates the importance of PP2A in efficient replication of various IAV subtypes, as decreased PP2Ac levels result in reduced cell viability and increased cell death after IAV infection. This is attributed to a synergistic action of hyper-activated PI3K/Akt, MAPK/JAK-STAT, and NF-kB signaling pathways related to apoptosis, indicating the critical role of PP2A in orchestrating cell survival mechanisms during IAV infection.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Review
Biochemistry & Molecular Biology
E. C. Dacol, S. Wang, Y. Chen, A. P. Lepique
Summary: Loss of function of tumor suppressor proteins in cancer cells is often the result of genetic mutations. Protein Phosphatase 2A (PP2A) is a tumor suppressor that is inactivated by endogenous inhibitors, leading to sustained activation of mitogenic signaling pathways. One of these inhibitors, SET, interacts with PP2A and is associated with high expression in various cancers, suggesting disruption of SET-PP2A interaction as a potential therapeutic strategy.
BIOCHIMICA ET BIOPHYSICA ACTA-REVIEWS ON CANCER
(2021)
Article
Neurosciences
Keunjung Heo, Himanish Basu, Amos Gutnick, Wei Wei, Evgeny Shlevkov, Thomas L. Schwarz
Summary: Microtubule-based transport is crucial for neuronal health by delivering mitochondria to distant regions of neurons. In this study, two compounds, indirubin and cantharidin, were identified to enhance mitochondrial motility in rat cortical neurons through a high-throughput screening. Further experiments demonstrated the importance of protein phosphatase 2A (PP2A) as a regulator of mitochondrial motility and suggested that cantharidin's effect may be mediated by PP2A.
FRONTIERS IN CELLULAR NEUROSCIENCE
(2022)
Article
Biochemistry & Molecular Biology
Brian Soto, Huma Ahmed, Meshach Pillai, Sangmi S. Park, Magdalena Ploszaj, Joshua Reece, Harsha Taluru, Dylan Bobrow, Howard Yu, Pascale Lafortune, Bakr Jundi, Louis Costanzo, Abdoulaye J. Dabo, Robert F. Foronjy, Christian Mueller, Michael Ohlmeyer, Patrick Geraghty
Summary: The study finds that the activity of PP2A in two models of emphysema can be restored using next-generation PP2A activators, which reduces inflammation cell infiltration and improves lung function. Activation of PP2A can also decrease the release of specific factors in the airways, leading to reduced neutrophil lung infiltration.
AMERICAN JOURNAL OF RESPIRATORY CELL AND MOLECULAR BIOLOGY
(2023)
Article
Cardiac & Cardiovascular Systems
Jordi Heijman, Xiaobo Zhou, Stefano Morotti, Cristina E. Molina, Issam H. Abu-Taha, Marcel Tekook, Thomas Jespersen, Yiqiao Zhang, Shokoufeh Dobrev, Hendrik Milting, Jan Gummert, Matthias Karck, Markus Kamler, Ali El-Armouche, Arnela Saljic, Eleonora Grandi, Stanley Nattel, Dobromir Dobrev
Summary: This study found that patients with atrial fibrillation (AF) have higher SK-channel current (I-SK) in their heart cells, and the antiarrhythmic drug apamin can significantly prolong the action potential of these cells. In addition, the study also found that the abundance of SK2 channel on the cell membrane is higher in AF patients. It was discovered that inhibiting the phosphatase-2A-dependent calmodulin-Thr80 dephosphorylation and promoting the trafficking and targeting of SK-channel subunits can enhance the function of SK channels.
CIRCULATION RESEARCH
(2023)
Article
Oncology
Laura Bownes, Raoud Marayati, Colin H. Quinn, Andee M. Beierle, Sara C. Hutchins, Janet R. Julson, Michael H. Erwin, Jerry E. Stewart, Elizabeth Mroczek-Musulman, Michael Ohlmeyer, Jamie M. Aye, Karina J. Yoon, Elizabeth A. Beierle
Summary: This study aimed to investigate the effects of two novel PP2A activators, ATUX-792 and DBK-1154, on neuroblastoma. The results showed that both compounds could activate PP2A and decrease cell survival, proliferation, and motility in neuroblastoma cells. In a mouse model, treatment with ATUX-792 also led to tumor necrosis and decreased tumor growth. These findings suggest a potential therapeutic role for these novel PP2A activators in neuroblastoma.
Article
Gastroenterology & Hepatology
Gangarao Davuluri, Nicole Welch, Jinendiran Sekar, Mahesha Gangadhariah, Khaled Alsabbagh Alchirazi, Maradumane L. Mohan, Avinash Kumar, Sashi Kant, Samjhana Thapaliya, McKenzie Stine, Megan R. McMullen, Rebecca L. McCullough, George R. Stark, Laura E. Nagy, Sathyamangla V. Naga Prasad, Srinivasan Dasarathy
Summary: Despite the high clinical significance of sarcopenia in alcohol-associated cirrhosis, the mechanisms of ethanol-induced impaired protein homeostasis are poorly understood. This study identified PP2A as a key mediator in ethanol-induced dysregulation of protein balance, suggesting potential therapeutic approaches targeting the PI3K gamma-PP2A axis.
Review
Cell Biology
Nicola M. Sergienko, Daniel G. Donner, Lea M. D. Delbridge, Julie R. McMullen, Kate L. Weeks
Summary: Protein phosphatase 2A (PP2A) is an important regulator of phosphoprotein homeostasis and plays a critical role in cardiac physiology and disease. It targets phosphoprotein substrates in a specific manner and its dysregulation has been observed in cardiac diseases.
CELLULAR SIGNALLING
(2022)
Article
Multidisciplinary Sciences
Stefan Schuechner, Peter Andorfer, Ingrid Mudrak, Egon Ogris
SCIENTIFIC REPORTS
(2016)
Letter
Pathology
Egon Ogris, Estelle Sontag, Brian Wadzinski, Goutham Narla
Article
Biochemistry & Molecular Biology
Ha Yin Lee, Yoko Itahana, Stefan Schuechner, Masahiro Fukuda, H. Shawn Je, Egon Ogris, David M. Virshup, Koji Itahana
Article
Biochemistry & Molecular Biology
Ha Yin Lee, Yoko Itahana, Stefan Schuechner, Masahiro Fukuda, H. Shawn Je, Egon Ogris, David M. Virshup, Koji Itahana
Article
Multidisciplinary Sciences
Ryotaro Yabe, Akane Miura, Tatsuya Usui, Ingrid Mudrak, Egon Ogris, Takashi Ohama, Koichi Sato
Article
Biochemistry & Molecular Biology
Ingrid E. Frohner, Ingrid Mudrak, Stephanie Kronlachner, Stefan Schuechner, Egon Ogris
Article
Biochemistry & Molecular Biology
Stefan Schuechner, Christian Behm, Ingrid Mudrak, Egon Ogris
Article
Multidisciplinary Sciences
Gregory Charles Nordmann, Erich Pascal Malkemper, Lukas Landler, Lyubov Ushakova, Simon Nimpf, Robert Heinen, Stefan Schuechner, Egon Ogris, David Anthony Keays
SCIENTIFIC REPORTS
(2020)
Article
Cell Biology
Ingrid E. Frohner, Ingrid Mudrak, Stefan Schuechner, Dorothea Anrather, Markus Hartl, Jean-Marie Sontag, Estelle Sontag, Brian E. Wadzinski, Teresa Preglej, Wilfried Ellmeier, Egon Ogris
Article
Biochemistry & Molecular Biology
Daniel Leonard, Wei Huang, Sudeh Izadmehr, Caitlin M. O'Connor, Danica D. Wiredja, Zhizhi Wang, Nilesh Zaware, Yinghua Chen, Daniela M. Schlatzer, Janna Kiselar, Nikhil Vasireddi, Stefan Schuechner, Abbey L. Perl, Matthew D. Galsky, Wenqing Xu, David L. Brautigan, Egon Ogris, Derek J. Taylor, Goutham Narla
Article
Multidisciplinary Sciences
Tobias Hochstoeger, Tarek Al Said, Dante Maestre, Florian Walter, Alexandra Vilceanu, Miriam Pedron, Thomas D. Cushion, William Snider, Simon Nimpf, Gregory Charles Nordmann, Lukas Landler, Nathaniel Edelman, Lennard Kruppa, Gerhard Duernberger, Karl Mechtler, Stefan Schuechner, Egon Ogris, E. Pascal Malkemper, Stefan Weber, Erik Schleicher, David A. Keays
Article
Multidisciplinary Sciences
Johanna E. Mayrhofer, Florian Enzler, Andreas Feichtner, Ruth Roeck, Jakob Fleischmann, Andrea Raffeiner, Philipp Tschaikner, Egon Ogris, Roland G. Huber, Markus Hartl, Rainer Schneider, Jakob Troppmair, Omar Torres-Quesada, Eduard Stefan
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2020)
Article
Biochemistry & Molecular Biology
David Maria Hollenstein, Gabriela Gerecova, Natalie Romanov, Jessica Ferrari, Jiri Veis, Marion Janschitz, Reinhard Beyer, Christoph Schueller, Egon Ogris, Markus Hartl, Gustav Ammerer, Wolfgang Reiter
Summary: This study reveals a signaling mechanism in which phosphatase-driven induction of phosphorylation occurs, with the protein phosphatase PP2A(Cdc55) acting as the main downstream effector in stress response pathways independent of kinase activation. This response affects multiple cellular processes and is crucial for stress survival. This demonstrates a previously unrecognized role of phosphatases in shaping the phosphorylome.
Article
Multidisciplinary Sciences
Spencer D. Balay, Tobias Hochstoeger, Alexandra Vilceanu, E. Pascal Malkemper, William Snider, Gerhard Duernberger, Karl Mechtler, Stefan Schuechner, Egon Ogris, Gregory C. Nordmann, Lyubov Ushakova, Simon Nimpf, David A. Keays
Summary: Research on the pigeon retina revealed two distinct transcript variants of clCRY2, with clCRY2a distributed throughout all retinal layers and clCRY2b enriched in the inner and outer nuclear layers. Proteomic analysis showed that clCRY2a/b interacts with typical circadian molecules, cell junction proteins, and components associated with the microtubule motor dynein.
SCIENTIFIC REPORTS
(2021)
Article
Microbiology
D. M. Hollenstein, J. Veis, N. Romanov, G. Gerecova, E. Ogris, M. Hartl, G. Ammerer, W. Reiter
Summary: A protein phosphatase PP2A(Rts1) plays a crucial role in the stress response of Saccharomyces cerevisiae, affecting the phosphorylation status of putative substrate proteins and antagonizing Rck2 signaling, which is regulated by the MAPKAP kinase.
MICROBIOLOGICAL RESEARCH
(2022)
Article
Biochemistry & Molecular Biology
Pei-Yang Gao, Ya-Nan Ou, Yi-Ming Huang, Zhi-Bo Wang, Yan Fu, Ya-Hui Ma, Qiong-Yao Li, Li-Yun Ma, Rui-Ping Cui, Yin-Chu Mi, Lan Tan, Jin-Tai Yu
Summary: Liver function may play a role in the progression of Alzheimer's disease. The study found that as AD progressed, certain liver function markers increased while others decreased. The relationship between liver function and CSF AD biomarkers indicates a potential mediation effect on cognition.
JOURNAL OF NEUROCHEMISTRY
(2024)