Kinases Phosphatases, Volume 3, Issue 1 (March 2025) – 6 articles

Protein phosphatase 2A (PP2A) is a highly conserved heterotrimeric enzyme complex present in all eukaryotic cells, consisting of a scaffolding A subunit, a catalytic C subunit, and a regulatory B subunit. The A and C subunits form the core enzyme, which interacts with the B subunit to determine the substrate specificity, subcellular localization, and enzymatic activity of the holoenzyme. The Arabidopsis thaliana genome encodes five C subunits, three A subunits, and 17 B subunits, enabling the formation of diverse holoenzymes with extensive functional versatility. Genetic evidence highlights the essential role of PP2A in regulating various physiological processes in plants, including responses to abiotic and biotic stresses and developmental programs. Notably, PP2A can act as both a positive and negative regulator within the same pathway, while individual subunits often participate in multiple processes. This functional diversity arises from the structural flexibility of PP2A. This review examines the structural diversity of plant PP2A and its regulatory roles across diverse physiological contexts. Full article

Coronavirus disease 2019 is a multi-systemic syndrome that caused a pandemic. Proteomic studies have shown changes in protein expression and interaction involved in signaling pathways related to SARS-CoV-2 infections. Protein phosphatases play a crucial role in regulating cell signaling. In this study, we assessed the potential involvement of protein phosphatases and their associated signaling pathways during SARS-CoV-2 infection by conducting a meta-analysis of proteome databases from COVID-19 patients. We identified both direct and indirect interactions between human protein phosphatases and viral proteins, as well as the expression levels and phosphorylation status of intermediate proteins. Our analyses revealed that PPP2CA and PTEN are key phosphatases involved in cell cycle and apoptosis regulation during SARS-CoV-2 infection. We also highlighted the direct involvement of PPP2CA in the cell division throughout its interaction with CDC20 protein (cell division cycle protein 20 homolog). This evidence strongly suggests that both proteins play critical roles during SARS-CoV-2 infection and represent potential targets for COVID-19 treatment. Full article

Phosphodegrons are critical motifs that play a pivotal role in the regulation of protein stability and function via phosphorylation-dependent signaling pathways. These motifs serve as recognition elements for ubiquitin ligases, facilitating the targeted degradation of proteins. By modulating key cellular processes such as cell cycle progression, DNA repair, and apoptosis, phosphodegrons are essential for maintaining cellular homeostasis. Dysregulation of phosphodegrons has been implicated in a wide range of diseases, including cancer and neurodegenerative disorders, highlighting their potential as therapeutic targets. This review provides an overview of phosphodegron functions along with their biological significance in health and disease. Additionally, we discuss current methodologies for studying phosphodegrons and explore emerging trends in their identification and therapeutic targeting. By synthesizing recent advances in the field, this article aims to offer insights into the future directions and challenges in phosphodegron research, ultimately underscoring their importance in cellular regulation and disease pathology. Full article

Tribbles Pseudokinase 3 (TRIB3) is a negative regulator of cellular signaling, particularly the PI3K-Akt and NF-κB pathways. Aberrant TRIB3 expressions have been reported in a number of cancers, but its role in tumor growth and progression remains controversial since both oncogenic and tumor suppressive activities have been reported. The goal of this study is to understand the roles of TRIB3 in prostate cancers through bioinformatic queries of public databases and experimental evaluations through gain-of-function and loss-of-function approaches. Here we report that there was increased TRIB3 gene expression with a Z-score over 2, relative to normal samples, in 26% of prostate cancers. Increased TRIB3 expression was associated with increased mutation counts and aneuploidy scores of prostate cancers. Increased TRIB3 expression was also associated with reduced progression-free or disease-free survival of prostate cancer patients. However, our experiments found that increased TRIB3 expression actually had an antiproliferative effect and increased cell cycle arrest at the G2/M phase. Depletion of the endogenous TRIB3 expression enhanced cell proliferation and reduced the level of Cdc25C phosphatase. Our results suggest that although TRIB3 expression was increased in prostate cancers in association with increased genomic instabilities, TRIB3 actually promoted cell cycle arrest and reduced tumor cell proliferation. Full article

Freeze tolerance is a remarkable adaptive trait exhibited by wood frogs (Rana sylvatica) during their hibernation period. To show the epigenetic mechanisms that contribute to kidney protection during freezing stress, this present study provides the first investigation of the role and dynamics of histone arginine methylation and the expression of protein arginine methyltransferases (PRMTs) in a freeze-tolerant vertebrate. Kidney samples from three groups were assessed: (a) control frogs acclimated at 5 °C, (b) 24 h frozen frogs, and (c) 8 h thawed frogs. Our findings revealed significant downregulation of PRMT1, PRMT3, and PRMT5 in kidneys from frozen wood frogs compared to the control group. This downregulation indicates a potential role for PRMT enzymes in the regulation of arginine methylation under freezing stress. In addition, we observed distinct changes in histone marks. H3R17me2a showed significant upregulation after 24 h of freezing, potentially indicating its involvement in the activation of genes related to freezing survival. By contrast, H3R26me2a was downregulated after both 24 h freezing and 8 h thawing, whereas H3R8me2a showed sustained levels after freezing but was downregulated after thawing. These findings highlight the dynamic nature of histone arginine methylation and PRMT expression in wood frog kidneys during freezing–thawing. Our results indicate that epigenetic modifications play a crucial role in shaping the adaptive responses of wood frog kidneys to freezing stress and contribute new information on the underlying biochemical modifications that support vertebrate freeze tolerance. Full article