Yamano, H. | Search bioRxiv

bioRxiv2025

The Balance between B55α and Greatwall expression levels predicts sensitivity to Greatwall inhibition in cancer cells

The Greatwall kinase inhibits PP2A-B55 phosphatase activity during mitosis to stabilise critical Cdk1-driven mitotic phosphorylation. Although Greatwall represents a potential oncogene and prospective therapeutic target, our understanding of cellular and molecular consequences of chemical Greatwall inactivation remains limited. To address this, we introduce C-604, a highly selective Greatwall inhibitor, and characterise both immediate and long-term cellular responses to the chemical attenuation of Greatwall activity. We demonstrate that Greatwall inhibition causes systemic destabilisation of the mitotic phosphoproteome, premature mitotic exit and pleiotropic cellular pathologies. Importantly, we demonstrate that the cellular and molecular abnormalities linked to reduced Greatwall activity are specifically dependent on the B55 isoform rather than other B55 variants, underscoring PP2A-B55 phosphatases as key mediators of cytotoxic effects of Greatwall-targeting agents in human cells. Additionally, we show that sensitivity to Greatwall inhibition varies in different cell line models and that dependency on Greatwall activity reflects the balance between Greatwall and B55 expression levels. Our findings highlight Greatwall dependency as a cell-specific vulnerability and propose the B55-to-Greatwall expression ratio as a predictive biomarker of cellular responses to Greatwall-targeted therapeutics.

cell biology↗

bioRxiv2017

High-resolution modeling of thermal thresholds and multiple environmental influences on coral bleaching for regional and local reef managements

Corals are one of the communities most threatened by global and local stressors. Excessive summer sea temperatures can cause coral bleaching, resulting in decreases in living coral coverage. Coral bleaching may begin with rising sea temperatures, although the widely used threshold of 1 {degrees}C over the local climatological maximum sea temperature has been reconsidered. In this study, we refine thermal indices predicting coral bleaching at high resolution (1 km) by statistically optimizing the thermal threshold and multiple environmental influences on bleaching, such as ultraviolet (UV) radiation, water turbidity, and cooling effects on corals. We use a dataset of coral bleaching events observed during 2004-2016 in Japan derived from the Web-based monitoring system, the Sango (Coral) Map Project, aiming at regional to local conservation of Japanese corals. We show how the ability to predict coral bleaching is improved by the choice of thermal index, statistical optimization of thermal thresholds, usage of multiple environmental influences, and modeling methods (generalized linear model and random forest). After optimization, the differences among the thermal indices in the ability to predict coral bleaching were slight. Among environmental influences, cooling effects, UV radiation, and water turbidity, in addition to a thermal index, well explain the occurrence of coral bleaching. Prediction based on the best explanatory model reveals that recent Japanese coral reefs are experiencing bleaching in many areas, although we show a practical way to reduce bleaching frequency significantly by screening UV radiation. Thus, our high-resolution models may provide a quantitative basis for the management of local reefs under current global and local stressors. The results of this study may be useful to other researchers for selecting a predictive method according to their needs or skills.

ecology↗