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
Irina O. Averkina, Ivan A. Paponov, Jose J. Sanchez-Serrano, Cathrine Lillo
Summary: This study investigated the role of PROTEIN PHOSPHATASE 2A (PP2A) in plant growth responses induced by plant growth-promoting rhizobacteria (PGPR). The findings suggest that PP2A, particularly the catalytic subunits C2 and C5, play a significant role in mediating the positive effects of PGPR on root and shoot growth. Comparison of different mutants indicated that plants with low PP2A activity exhibit a more pronounced response to PGPR treatment.
Article
Biochemistry & Molecular Biology
Hyuk Sung Yoon, Kaien Fujino, Shenkui Liu, Tetsuo Takano, Daisuke Tsugama
Summary: The study shows that Arabidopsis PP2A B''-family subunits interact with PP2A A (scaffold) subunits and can mediate VIP1 dephosphorylation. This provides important insights into the molecular mechanism of VIP1 dephosphorylation.
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
(2021)
Article
Pharmacology & Pharmacy
Sandy Elsayed, Khaled A. Elsaid
Summary: This study found that PP2A activity is inactivated by ROS in acute gout, and a PP2A activator exhibits broad anti-inflammatory effects. In in vitro and in vivo experiments, fingolimod reduced the generation of UA and ROS, inhibited XO activity, and decreased IL-1 beta secretion.
FRONTIERS IN PHARMACOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Ni-Chen Chang, Quirze Rovira, Jonathan Wells, Cedric Feschotte, Juan M. Vaquerizas
Summary: This study describes the demography and genomic distribution of zebrafish transposable elements (TEs) and their expression during embryogenesis. The results reveal a highly dynamic genomic ecosystem comprising nearly 2000 distinct TE families, with longer retroelements being retained in intergenic regions and shorter elements more frequently found near or within genes. The study provides a valuable resource for using zebrafish as a model to study the impact of TEs on vertebrate development.
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
Neurosciences
Mohammad Hleihil, Karthik Balakrishnan, Dietmar Benke
Summary: The study reveals the important role of protein phosphatase 2A (PP2A) in regulating the cell surface expression of GABA(B) receptors, particularly under conditions associated with excitotoxicity. By inhibiting receptor recycling and promoting receptor degradation, PP2A downregulates the cell surface expression of GABA(B) receptors. The use of an interfering peptide (PP2A-Pep) restores the expression of GABA(B) receptors and inhibits neuronal death. These findings suggest that interference with the interaction between GABA(B) receptors and PP2A could be a promising strategy for treating neurological diseases associated with imbalances in excitation/inhibition and downregulation of GABA(B) receptors.
FRONTIERS IN MOLECULAR NEUROSCIENCE
(2022)
Review
Cell Biology
Sarah A. Welsh, Alessandro Gardini
Summary: Integrator, as the only metazoan-specific RNA polymerase II (Pol II)-associated large multisubunit complex, plays essential roles in processing non-coding RNAs and regulating Pol II promoter-proximal pausing and elongation. It has diverse functions in development and tumorigenesis. Recent studies have revealed its involvement in transcription, RNA processing, chromatin landscape, and DNA repair.
NATURE REVIEWS MOLECULAR CELL BIOLOGY
(2023)
Article
Cell Biology
Balint Becsi, Zoltan Konya, Anita Boratko, Katalin Kovacs, Ferenc Erdodi
Summary: EGCG acts as an agonist of 67LR to inhibit adipogenesis via the activation of PP2A and suppression of MP. These effects result in reduced lipid droplet formation, changes in cell shape, and decreased lipid accumulation.
Article
Ecology
Soichiro Nishiyama, Mao Fujikawa, Hisayo Yamane, Kenta Shirasawa, Ebrahiem Babiker, Ryutaro Tao
Summary: Interspecific hybridization is a common breeding approach for introducing novel traits and genetic diversity. The study found that rabbiteye blueberry cultivars were genetically distinct from southern highbush blueberry and northern highbush blueberry cultivars, with the latter two being genetically indistinguishable. The allele selection strategies used by breeders may have influenced the genetic differentiation between the species.
Article
Agriculture, Dairy & Animal Science
Jiazheng Xie, Yi Zhang
Summary: This study conducted a systematic survey and analysis of mite contaminations in the public genomic database for the first time. It found that mite contamination is not rare and discussed the host associations and evolution of mites based on the contaminated contigs.
Article
Microbiology
Pir Tariq Shah, Amina Nawal Bahoussi, Xiaogang Cui, Shaista Shabir, Changxin Wu, Li Xing
Summary: Chicken infectious anemia (CIA) is a highly immunosuppressive disease in young chickens, causing aplastic anemia, growth retardation, and lymphoid tissue atrophy. The disease is caused by chicken anemia virus (CAV), belonging to the genus Gyrovirus, family Anelloviridae. Through genome analysis and phylogeographic study, this research identified two major clades, GI and GII, with multiple sub-clades, and traced the spread of CAV from Japan to China, China to Egypt, and subsequently to other countries. The study also discovered recombination events and significant amino acid variability in CAV genomes, providing valuable insights for understanding the evolutionary history and implementing preventive measures against CAVs.
FRONTIERS IN MICROBIOLOGY
(2023)
Article
Plant Sciences
Kyaw Myo Aung, Win Htet Oo, Thant Zin Maung, Myeong-Hyeon Min, Aueangporn Somsri, Jungrye Nam, Kyu-Won Kim, Bhagwat Nawade, Chang-Yong Lee, Sang-Ho Chu, Yong-Jin Park
Summary: This study investigated the genetic variation of the OsTPP7 gene, which is associated with flood tolerance in rice. The results showed that the temperate japonica ecotype had the highest coleoptile length under both normal and flooded conditions, indicating the possibility of balancing selection or population expansion in indica, admixture, and tropical japonica ecotypes. A total of 18 haplotypes were identified, with three in cultivated accessions, 13 in the wild type, and two in both. Phenotypic analysis revealed significant differences in flooded coleoptile length and tolerance between major haplotypes. These findings have important implications for future selective breeding and the development of efficient haplotype-based breeding strategies for flood tolerance improvement.
FRONTIERS IN PLANT SCIENCE
(2023)
Review
Agronomy
Helmuth E. E. Nieves-Orduna, Konstantin V. V. Krutovsky, Oliver Gailing
Summary: The cacao tree is cultivated in the tropics to produce seeds, which are valuable raw materials for the chocolate industry. It is crucial to conserve and use cacao genetic resources for breeding programs to enhance yield, improve quality, and disease resistance. This review focuses on three important aspects of cacao genetics necessary for sustainable production and crop improvement: geographic distribution and genetic variation of wild cacao populations, conservation and utilization of cacao genetic resources, and genetic basis of agronomic traits and its application for cacao improvement. We also emphasize the critical research areas required for sustainable cacao cultivation.
Article
Environmental Sciences
Huiqun Yu, Jiyuan Cui, Yixue Xu, Li-Juan Feng, Wansong Zong
Summary: Biotransformation is recognized as an effective pathway to regulate the environmental risk of microcystins (MCs). The inhibition effects of MCLR-biotransformation products (MCLR-BTPs) on protein phosphatase 2A (PP2A) were evaluated, and it was found that biotransformation effectively regulated MCLR toxicity. By introducing biothiols, the covalent binding between MCLR and PP2A was blocked, restoring the catalytic activity of PP2A.
INTERNATIONAL JOURNAL OF ENVIRONMENTAL RESEARCH AND PUBLIC HEALTH
(2023)
Article
Multidisciplinary Sciences
Ievgenia Pastushenko, Federico Mauri, Yura Song, Florian de Cock, Bob Meeusen, Benjamin Swedlund, Francis Impens, Delphi Van Haver, Matthieu Opitz, Manuel Thery, Yacine Bareche, Gaelle Lapouge, Marjorie Vermeersch, Yves-Remi Van Eycke, Cedric Balsat, Christine Decaestecker, Youri Sokolow, Sergio Hassid, Alicia Perez-Bustillo, Beatriz Agreda-Moreno, Luis Rios-Buceta, Pedro Jaen, Pedro Redondo, Ramon Sieira-Gil, Jose F. Millan-Cayetano, Onofre Sanmatrtin, Nicky D'Haene, Virginie Moers, Milena Rozzi, Jeremy Blondeau, Sophie Lemaire, Samuel Scozzaro, Veerle Janssens, Magdalena De Troya, Christine Dubois, David Perez-Morga, Isabelle Salmon, Christos Sotiriou, Francoise Helmbacher, Cedric Blanpain
Summary: This study reveals that mutation of the FAT1 gene promotes tumor initiation, progression, invasiveness, stemness, and metastasis. Loss of function of FAT1 activates a CAMK2-CD44-SRC axis while inactivates EZH2, playing important roles in the expression of YAP1 and ZEB1.
Review
Biochemistry & Molecular Biology
Iris Verbinnen, Pieter Vaneynde, Sara Reynhout, Lisa Lenaerts, Rita Derua, Gunnar Houge, Veerle Janssens
Summary: In this review, the authors examine the impact of PP2A gene mutations on neurodevelopmental disorders and intellectual disability, with a focus on PPP2CA, PPP2R1A, and PPP2R5D. They provide insights into how these mutations affect PP2A structure, substrate specificity, and potential function in neurobiology and brain development.
BIOCHEMICAL SOCIETY TRANSACTIONS
(2021)
Article
Oncology
Bob Meeusen, Emanuela Elsa Cortesi, Judit Domenech Omella, Anna Sablina, Juan-Jose Ventura, Veerle Janssens
Summary: This study found that the loss of PP2A activator PTPA in KRAS-mutant lung adenocarcinomas is associated with poorer overall survival, increased cell growth, and accelerated tumor formation. Additionally, the depletion of PPP2R4 induced resistance against MEK inhibitor but sensitized cells to mTOR inhibitor, highlighting its clinical relevance in NSCLC etiology and kinase inhibitor response.
Article
Cell Biology
Emanuela E. Cortesi, Bob Meeusen, Arno Vanstapel, Stijn E. Verleden, Bart M. Vanaudenaerde, Wim A. Wuyts, Wim Janssens, Veerle Janssens, Tania Roskams, Juan-Jose Ventura
Summary: Research indicates an elevated expression of LGR6 in abnormal lung epithelial progenitors in chronic obstructive pulmonary disease (COPD) and idiopathic pulmonary fibrosis (IPF), with an increase in senescence-associated markers in these cells. Through chronic activation of the Wnt/beta-catenin pathway, LGR6 mediates the impairment and exhaustion of epithelial progenitors in both diseases.
Article
Genetics & Heredity
Nora Oyama, Pieter Vaneynde, Sara Reynhout, Emily M. Pao, Andrew Timms, Xiao Fan, Kimberly Foss, Rita Derua, Veerle Janssens, Wendy Chung, Ghayda M. Mirzaa
Summary: This study delineates the common features of PPP2R5D-related neurodevelopmental disorders, expands the clinical and molecular spectrum, and identifies genotype-phenotype correlations.
JOURNAL OF MEDICAL GENETICS
(2023)
Review
Cell Biology
Pieter Vaneynde, Iris Verbinnen, Veerle Janssens
Summary: Reversible protein phosphorylation is a fundamental regulatory mechanism in eukaryotic cell and organismal physiology. Mutations in serine/threonine protein phosphatases (PSP) have been found to be associated with congenital diseases, most of which are characterized by brain-specific abnormalities. Understanding the pathogenic mechanisms of these diseases and identifying downstream targets and effectors could potentially lead to new therapeutic approaches.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2022)
Article
Cell Biology
Iris Verbinnen, Sara S. S. Procknow, Lisa Lenaerts, Sara Reynhout, Aujan Mehregan, Chris Ulens, Veerle Janssens, Katherine A. A. King
Summary: PP2A-related (neuro) developmental disorders are genetic diseases caused by genetic alterations in the genes encoding subunits of type 2A protein phosphatases. This study reports a case of PPP2CA-affected individual with a novel de novo missense variant, and evaluates its pathogenicity. Clinically, the patient presented with developmental delay, dysmorphic facial features, seizures, and autistic behaviors. This study reveals a milder manifestation of clinical and molecular spectrum in PPP2CA cases.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2022)
Article
Chemistry, Medicinal
Raquel L. Arribas, Lucia Viejo, Isaac Bravo, Minerva Martinez, Eva Ramos, Alejandro Romero, Eva M. Garcia-Frutos, Veerle Janssens, Carmen Montiel, Cristobal de los Rios
Summary: Protein phosphatase 2A (PP2A) plays a crucial role in cellular processes and its deficiency is associated with severe pathologies. In Alzheimer's disease, the hyperphosphorylation of tau protein is linked to the depression of PP2A activity. Researchers have designed new ligands to prevent PP2A inhibition, with compound 10 showing the most promising outcomes.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Article
Medicine, Research & Experimental
Jos van Pelt, Bob Meeusen, Rita Derua, Liesbeth Guffens, Eric Van Cutsem, Veerle Janssens, Chris Verslype
Summary: Pancreatic ductal adenocarcinoma (PDAC) has a low survival and little therapeutic advancements are expected. Epithelial-to-Mesenchymal transition (EMT) and Protein Phosphatase Type 2A (PP2A) play a role in aggressive PDAC. This study investigates the relationship between PP2A expression signature and EMT, and explores treatment implications.
JOURNAL OF TRANSLATIONAL MEDICINE
(2023)
Article
Multidisciplinary Sciences
Karolina Pavic, Nikhil Gupta, Judit Domenech Omella, Rita Derua, Anna Aakula, Riikka Huhtaniemi, Juha A. Maatta, Nico Hofflin, Juha Okkeri, Zhizhi Wang, Otto Kauko, Roosa Varjus, Henrik Honkanen, Daniel Abankwa, Maja Kohn, Vesa P. Hytonen, Wenqing Xu, Jakob Nilsson, Rebecca Page, Veerle Janssens, Alexander Leitner, Jukka Westermarck
Summary: This study reveals the molecular level details and structural mechanisms of PP2A-B56 alpha inhibition by the oncoprotein CIP2A. CIP2A displaces the PP2A-A subunit and forms a pseudotrimer, blocking the B56 alpha substrate binding site and stabilizing CIP2A protein.
NATURE COMMUNICATIONS
(2023)
Article
Oncology
Judit Domenech Omella, Emanuela E. Cortesi, Iris Verbinnen, Michiel Remmerie, Hanghang Wu, Francisco J. Cubero, Tania Roskams, Veerle Janssens
Summary: The deletion of Ppp2r5d gene accelerates the development of hepatocellular carcinoma (HCC) in a mouse model of DEN-induced hepatocarcinogenesis, suggesting its tumor-suppressive function. The deletion of Ppp2r5d also leads to the development of HCC and combined hepatocellular-cholangiocarcinoma (cHCC-CCA), and may regulate its own expression to restrict tumor growth.
Editorial Material
Cell Biology
Veerle Janssens, Brian E. Wadzinski, Chenchen Li, Richard E. Honkanen
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2023)
Meeting Abstract
Gastroenterology & Hepatology
Judit Domenech Omella, Bob Meeusen, Emanuela Cortesi, Karen Zwaenepoel, Rita Derua, Chris Verslype, Patrick Pauwels, Jukka Westermarck, Tania Roskams, Jos van Pelt, Veerle Janssens
JOURNAL OF HEPATOLOGY
(2022)
Article
Nutrition & Dietetics
Veronika Kloubert, Inga Wessels, Jana Wolf, Karoline Blaabjerg, Veerle Janssens, Jan Hapala, Wolfgang Wagner, Lothar Rink
Summary: The study revealed that zinc deficiency leads to reduced IL-2 expression in T cells due to enhanced PP2A and HDAC1 activity, and a molecular link through the transcription factor CREMa was uncovered in connecting zinc deficiency with this decreased IL-2 production.
CLINICAL NUTRITION
(2021)
Article
Genetics & Heredity
Lisa Lenaerts, Sara Reynhout, Iris Verbinnen, Frederic Laumonnier, Annick Toutain, Frederique Bonnet-Brilhault, Yana Hoorne, Shelagh Joss, Anna K. Chassevent, Constance Smith-Hicks, Bart Loeys, Pascal Joset, Katharina Steindl, Anita Rauch, Sarju G. Mehta, Wendy K. Chung, Koenraad Devriendt, Susan E. Holder, Tamison Jewett, Lauren M. Baldwin, William G. Wilson, Shelley Towner, Siddharth Srivastava, Hannah F. Johnson, Cornelia Daumer-Haas, Martina Baethmann, Anna Ruiz, Elisabeth Gabau, Vani Jain, Vinod Varghese, Ali Al-Beshri, Stephen Fulton, Oded Wechsberg, Naama Orenstein, Katrina Prescott, Anne-Marie Childs, Laurence Faivre, Sebastien Moutton, Jennifer A. Sullivan, Vandana Shashi, Suzanne M. Koudijs, Malou Heijligers, Emma Kivuva, Amy McTague, Alison Male, Yvette van Ierland, Barbara Plecko, Isabelle Maystadt, Rizwan Hamid, Vickie L. Hannig, Gunnar Houge, Veerle Janssens
Summary: We significantly expand the phenotypic spectrum of PPP2R1A-related NDD, revealing a broader clinical presentation of the patients and that the functional consequences of the variants are more diverse than previously reported.
GENETICS IN MEDICINE
(2021)