We have proposed computer-generated models of the catalytic subunits of the serine-threonine protein phosphatases PP1 and PP2A complexed with their endogenous substrate phospho-DARPP-32, and several known naturally occurring inhibitors. This study is part of an overall effort to elucidate the signal transduction pathways in which PP1 and PP2A may play an important role.
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http://dx.doi.org/10.1016/s0968-0896(97)00145-4 | DOI Listing |
Toxicol Rep
December 2024
Biochemistry Laboratory, Department of Zoology, School of Biological Sciences, Dr. Harisingh Gour Vishwavidyalaya (A Central University), Sagar, Madhya Pradesh 470003, India.
Cyanotoxins are primarily produced by different species of cyanobacteria, also known as blue-green algae, and have appeared to be environmental poisons that have various toxic effects on animal health, including humans. Cyanotoxins have been linked to the development and promotion of multiple cancers in recent studies. Important cyanotoxins, such as microcystins, nodularins, and cylindrospermopsin, have been found to play significant roles in developing and promoting various cancers.
View Article and Find Full Text PDFMol Cell
December 2024
Cancer Institute & Department of Radiation Oncology, Fudan University Shanghai Cancer Center, Institutes of Biomedical Sciences, State Key Laboratory of Genetic Engineering, Shanghai Key Laboratory of Medical Epigenetics, Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China. Electronic address:
RNA polymerase II progression from initiation to elongation is driven in part by a cascade of protein kinases acting on the core transcription machinery. Conversely, the corresponding phosphatases, notably PP2A and PP1-the most abundant serine-threonine phosphatases in cells-are thought to mainly impede polymerase progression, respectively restraining pause release at promoters and elongation at terminators. Here, we reveal an unexpected role of PP1, within the phosphatase 1 nuclear targeting subunit (PNUTS)-PP1 complex, in sustaining global transcriptional activation in human cells.
View Article and Find Full Text PDFNaunyn Schmiedebergs Arch Pharmacol
August 2024
Medical Faculty, Institute for Pharmacology and Toxicology, Martin Luther University Halle-Wittenberg, Halle (Saale), Germany.
Cantharidin and sodium fluoride inhibit the activity of serine/threonine protein phosphatases 1 (PP1) and 2A (PP2A) and increase the force of contraction in human atrial preparations. R-phenylisopropyl adenosine (R-PIA) acts as an agonist at A-adenosine receptors. R-PIA exerts a negative inotropic effect on human atria.
View Article and Find Full Text PDFToxicon
October 2024
Department of Pharmaceutical Sciences, Washington State University, Spokane, WA, 99202, United States. Electronic address:
Microcystin-LR (MCLR) exposure has been associated with development of hepatocellular carcinoma (HCC). Many of the carcinogenic mechanisms for MCLR have been attributed to the induction of cell survival and proliferation through altered protein phosphorylation pathways by inhibition of protein phosphatases 1 (PP1) and PP2A. The current study determined MCLR effects on the phosphoproteome in human HepaRG cells.
View Article and Find Full Text PDFbioRxiv
November 2024
McArdle Laboratory for Cancer Research, Department of Oncology, University of Wisconsin-Madison, Madison, Wisconsin, USA.
Virion Infectivity Factor (Vif) of the Human Immunodeficiency Virus type 1 (HIV-1) targets and degrades cellular APOBEC3 proteins, key regulators of intrinsic and innate antiretroviral immune responses, thereby facilitating HIV-1 infection. While Vif's role in degrading APOBEC3G is well-studied, Vif is also known to cause cell cycle arrest, but the detailed nature of Vif's effects on the cell cycle has yet to be delineated. In this study, we employed high-temporal single-cell live imaging and super-resolution microscopy to monitor individual cells during Vif-induced cell cycle arrest.
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