Fostriecin, an antitumor antibiotic with inhibitory activity against serine/threonine protein phosphatases types 1 (PP1) and 2A (PP2A), is highly selective for PP2A

Fostriecin, an antitumor antibiotic produced by Streptomyces pulveraceus, is a strong inhibitor of type 2A (PP2A; IC50 3.2 nM) and a weak inhibitor of type 1 (PP1; IC50 131 μM) serine/threonine protein phosphatases. Fostriecin has no apparent effect on the activity of PP2B, and dose‐inhibition studies conducted with whole cell homogenates indicate that fostriecin also inhibits the native forms of PP1 and PP2A. Studies with recombinant PP1/PP2A chimeras indicate that okadaic acid and fostriecin have different binding sites.

• Publication year

  1997

• Venue

  FEBS Letters

• Publication date

  1997-10-27

• Fields of study

  Biology, Medicine, Chemistry

• Identifiers
  DOI 10.1016/S0014-5793(97)01210-6PMID 9373158
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

• Studies on the biochemical mechanism of the novel antitumor agent, CI-920

  2004cited by this paper
• A Molecular Basis for Different Interactions of Marine Toxins with Protein Phosphatase-1

  1997cited by this paper
• Fostriecin: a review of the preclinical data.

  1997cited by this paper
• Site-directed mutagenesis of amino acid residues of protein phosphatase 1 involved in catalysis and inhibitor binding.

  1997cited by this paper
• Detection of DSP-toxins, okadaic acid, and dinophysis toxin-1 in shellfish by serine/threonine protein phosphatase assay.

  1996cited by this paper
• Mutational analysis of the catalytic subunit of muscle protein phosphatase-1.

  1996cited by this paper
• CANCER BIOLOGY: The antitumor drug fostriecin induces vimentin hyperphosphorylation and intermediate filament reorganization

  1996cited by this paper
• [21] Site-directed mutagenesis by PCR: Substitution, insertion, deletion, and gene fusion

  1995cited by this paper
• PROTEIN PHOSPHATASE INHIBITORY ACTIVITY IN EXTRACTS OF CULTURED BLUE‐GREEN ALGAE (CYANOPHYTA) 1

  1995cited by this paper
• Chromosome condensation induced by fostriecin does not require p34cdc2 kinase activity and histone H1 hyperphosphorylation, but is associated with enhanced histone H2A and H3 phosphorylation.

  1995cited by this paper
• Three-dimensional structure of the catalytic subunit of protein serine/threonine phosphatase-1

  1995cited by this paper
• Activation of protein kinases and inhibition of protein phosphatases play a central role in the regulation of exocytosis in mouse pancreatic beta cells.

  1994cited by this paper
• Characterization of deletion mutants of the catalytic subunit of protein phosphatase-1.

  1994cited by this paper
• Antitumor drug fostriecin inhibits the mitotic entry checkpoint and protein phosphatases 1 and 2A.

  1994cited by this paper
• Characterization of natural toxins with inhibitory activity against serine/threonine protein phosphatases.

  1994cited by this paper
• Characterization of serine/threonine protein phosphatases in RINm5F insulinoma cells

  1993cited by this paper
• Cantharidin, another natural toxin that inhibits the activity of serine/threonine protein phosphatases types 1 and 2A

  1993cited by this paper
• Tumor promotion by inhibitors of protein phosphatases 1 and 2A: the okadaic acid class of compounds.

  1993cited by this paper
• Cantharidin-binding protein: identification as protein phosphatase 2A.

  1992cited by this paper
• Hyperphosphorylation of cytokeratins 8 and 18 by microcystin-LR, a new liver tumor promoter, in primary cultured rat hepatocytes.

  1992cited by this paper
• Cyanobacterial nodularin is a potent inhibitor of type 1 and type 2A protein phosphatases.

  1991cited by this paper
• A novel protein phosphatase inhibitor, tautomycin Effect on smooth muscle

  1991cited by this paper
• Cyanobacterial microcystin‐LR is a potent and specific inhibitor of protein phosphatases 1 and 2A from both mammals and higher plants

  1990cited by this paper
• Okadaic acid: a new probe for the study of cellular regulation.

  1990cited by this paper
• Tautomycin from the bacterium Streptomyces verticillatus

  1990cited by this paper
• Characterization of microcystin-LR, a potent inhibitor of type 1 and type 2A protein phosphatases.

  1990cited by this paper
• Polyoma small and middle T antigens and SV40 small t antigen form stable complexes with protein phosphatase 2A.

  1990cited by this paper
• The structure of tautomycin, a dialkylmaleic anhydride antibiotic.

  1990cited by this paper
• Antitumor imide derivatives of 7-oxabicyclo[2.2.1]heptane-2,3-dimethyl-2,3-dicarboxylic acid.

  1989cited by this paper
• Calyculin A and okadaic acid: inhibitors of protein phosphatase activity.

  1989cited by this paper
• The structure and regulation of protein phosphatases.

  1989cited by this paper
• Methods to distinguish various types of protein phosphatase activity.

  1988cited by this paper
• Inhibitory effect of a marine-sponge toxin, okadaic acid, on protein phosphatases. Specificity and kinetics.

  1988cited by this paper
• Inhibition of type II topoisomerase by fostriecin.

  1988cited by this paper
• Naming of cyclic heptapeptide toxins of cyanobacteria (blue-green algae).

  1988cited by this paper
• In vitro activity of the novel antitumor antibiotic fostriecin (CI-920) in a human tumor cloning assay.

  1986cited by this paper
• The biochemical pharmacology of CI-920, a structurally novel antibiotic with antileukemic activity.

  1985cited by this paper
• Phosphorylase phosphatase catalytic subunit. Evidence that the Mr = 33,000 enzyme fragment is derived from a native protein of Mr = 70,000.

  1985cited by this paper
• Anticancer activity of the structurally novel antibiotic Cl-920 and its analogues.

  1984cited by this paper
• Transport of the antitumor antibiotic Cl-920 into L1210 leukemia cells by the reduced folate carrier system.

  1984cited by this paper
• Novel antitumor agents CI-920, PD 113,270 and PD 113,271. II. Isolation and characterization.

  1983cited by this paper
• Novel antitumor agents CI-920, PD 113,270 and PD 113,271. I. Taxonomy, fermentation and biological properties.

  1983cited by this paper
• Studies on antitumor actions of cantharidin.

  1980cited by this paper
• Purification and properties of bovine myocardial phosphorylase phosphatase (protein phosphatase C).

  1978cited by this paper

• Biologically Active Natural δ‐Lactones in Medicinal Chemistry: Structures, Bioactivities, and Synthesis

  2026cites this paper
• Isorhyncophylline Targets PP2AC to Modulate YAP to Inhibit Endothelial Cell Inflammation.

  2026cites this paper
• Formal Synthesis of Fostriecin via Asymmetric Alcohol-Mediated Carbonyl Allylation.

  2025cites this paper
• Concise Synthesis of Fostriecin and Analogs through Late-Stage Chemoenzymatic Installation of Their Key Pharmacophores.

  2025cites this paper
• Elucidation of roles of serine/threonine phosphatases PP1 and PP2A in mediating CCK-stimulated growth and enzyme secretion in pancreatic acinar cells.

  2025cites this paper
• Effects of Lysinibacillus sphaericus HY3 on the gut microbiota, metabolism and resistance to Aeromonas hydrophila infection of adult zebrafish (Danio rerio)

  2025cites this paper
• UHRF1 Controls the Timing of RAD51 Removal During DNA Damage Repair Through Suppressing RFWD3

  2025cites this paper
• A Protein Phosphatase 2A-Based Assay to Detect Okadaic Acids and Microcystins

  2024cites this paper
• Targeting phosphatases: From molecule design to clinical trials.

  2023cites this paper
• Cofilin activation in pancreatic acinar cells plays a pivotal convergent role for mediating CCK-stimulated enzyme secretion and growth

  2023influential citation
• Eukaryotic-like phosphoprotein phosphatase (PPP) enzyme evolution: interactions with environmental toxins and regulatory proteins

  2023cites this paper
• PP1, PP2A and PP2B Interplay in the Regulation of Sperm Motility: Lessons from Protein Phosphatase Inhibitors

  2022cites this paper
• Pleiotropy of PP2A Phosphatases in Cancer with a Focus on Glioblastoma IDH Wildtype

  2022cites this paper
• A bidirectional switch in the Shank3 phosphorylation state biases synapses toward up- or downscaling

  2021cites this paper
• High dietary potassium causes ubiquitin-dependent degradation of the kidney sodium-chloride cotransporter

  2021cites this paper
• Serine-threonine protein phosphatase regulation of Cx43 dephosphorylation in arrhythmogenic disorders.

  2021cites this paper
• Strategies for Targeting Serine/Threonine Protein Phosphatases with Small Molecules in Cancer.

  2021cites this paper
• A disorder-related variant (E420K) of a PP2A-regulatory subunit (PPP2R5D) causes constitutively active AKT-mTOR signaling and uncoordinated cell growth

  2021cites this paper
• Functionalization of Novel PP5 Inhibitors

  2021cites this paper
• The role of FoxO1 and its modulation with small molecules in the development of diabetes mellitus: A review

  2021cites this paper
• Activated Protein Phosphatase 2A Disrupts Nutrient Sensing Balance Between Mechanistic Target of Rapamycin Complex 1 and Adenosine Monophosphate–Activated Protein Kinase, Causing Sarcopenia in Alcohol‐Associated Liver Disease

  2020cites this paper
• Total and Formal Syntheses of Fostriecin.

  2020cites this paper
• LiP-Quant, an automated chemoproteomic approach to identify drug targets in complex proteomes

  2019cites this paper
• Regulation of Neuronal Na+/K+-ATPase by Specific Protein Kinases and Protein Phosphatases

  2019cites this paper
• Synthesis of Dehydro-Dephospho-Fostriecin and Formal Total Synthesis of Fostriecin.

  2019cites this paper
• Inhibitors of Serine/Threonine Protein Phosphatases: Biochemical and Structural Studies Provide Insight for Further Development.

  2019cites this paper
• To be or not to be: PP2A as a dual player in CNS functions, its role in neurodegeneration, and its interaction with brain insulin signaling

  2019cites this paper
• Dynamic Phosphorylation and Dephosphorylation of Cyclase-Associated Protein 1 by Antagonistic Signaling through Cyclin-Dependent Kinase 5 and cAMP Are Critical for the Protein Functions in Actin Filament Disassembly and Cell Adhesion

  2019influential citation
• Role of protein phosphatases PP1, PP2A, PP4 and Cdc14 in the DNA damage response

  2019cites this paper
• Autophosphorylated CaMKII Facilitates Spike Propagation in Rat Optic Nerve

  2018cites this paper
• Pharmacological approach to increasing the retention of radiation-induced γ-H2AX foci using phosphatase inhibitors: significance in radiation biodosimetry

  2018cites this paper
• Pharmacological approach to increase the retention of radiation induced gamma-H2AX foci using phosphatase inhibitors: significance in radiation biodosimetry.

  2018cites this paper
• Tonic ATP-mediated growth suppression in peripheral nerve glia requires arrestin-PP2 and is evaded in NF1

  2018cites this paper
• Novel mechanisms of HER2-targeted therapy resistance in breast cancer

  2018cites this paper
• ϵ-Polylysine-Capped Mesoporous Silica Nanoparticles as Carrier of the C9h Peptide to Induce Apoptosis in Cancer Cells.

  2018cites this paper
• The synthesis of mono-alkyl phosphates and their derivatives: an overview of their nature, preparation and use, including synthesis under plausible prebiotic conditions.

  2018cites this paper
• Antiphospholipid antibodies induce thrombosis by PP2A activation via apoER2-Dab2-SHC1 complex formation in endothelium.

  2018cites this paper
• An Ultra-High-Throughput Screen for Catalytic Inhibitors of Serine/Threonine Protein Phosphatases Types 1 and 5 (PP1C and PP5C)

  2017cites this paper
• Protein phosphatases 1 and 2A and their naturally occurring inhibitors: current topics in smooth muscle physiology and chemical biology

  2017cites this paper
• Correction to: Protein phosphatases 1 and 2A and their naturally occurring inhibitors: current topics in smooth muscle physiology and chemical biology

  2017cites this paper
• Regulation of cardiac gap junctions by protein phosphatases.

  2017influential citation
• Enzyme mediated kinetic resolution of δ-hydroxy-α,β-unsaturated esters as a route to optically active δ-lactones

  2017cites this paper
• Bioprobes at a Glance

  2017cites this paper
• Synthetic Strategies Employed for the Construction of Fostriecin and Related Natural Products.

  2016cites this paper
• Efficient production of recombinant PP2A at a low temperature using a baculovirus expression system

  2016cites this paper
• Protein phosphatase role in adenosine A1 receptor-induced AMPA receptor trafficking and rat hippocampal neuronal damage in hypoxia/reperfusion injury.

  2016cites this paper
• Hypothermic Preconditioning Reverses Tau Ontogenesis in Human Cortical Neurons and is Mimicked by Protein Phosphatase 2A Inhibition

  2015cites this paper
• Algal High-Value Consumer Products

  2015cites this paper
• DNA Topoisomerase II: Promising Target for Anticancer Drugs

  2015cites this paper
• Syntheses of natural 1,3-polyol/α-pyrone and its all stereoisomers to estimate antifungal activities against plant pathogenic fungi.

  2015cites this paper
• Force-inhibiting effect of Ser/Thr protein phosphatase 2A inhibitors on bovine ciliary muscle

  2015influential citation
• Protein phosphatase 2A regulates deoxycytidine kinase activity via Ser‐74 dephosphorylation

  2014cites this paper
• Synthesis and evaluation of (-)-Massoialactone and analogues as potential anticancer and anti-inflammatory agents.

  2014cites this paper
• Greatwall-phosphorylated Endosulfine is both an inhibitor and a substrate of PP2A-B55 heterotrimers

  2014cites this paper
• p38 mitogen-activated protein kinase and transcription factor GATA-4 in the regulation of cardiomyocyte function

  2014cites this paper
• 6.12 Inorganic Acid Derivatives

  2014cites this paper
• Regulation of hippocampal synaptic transmission and receptor trafficking by adenosine in hypoxia and ischemia: role of protein phosphatases 1, 2A and 2B, casein kinase 2 (CK2), and equilibrative nucleoside transporters (ENTs).

  2014cites this paper
• Evidence toward a Dual Phosphatase Mechanism That Restricts Aurora A (Thr-295) Phosphorylation during the Early Embryonic Cell Cycle*

  2014cites this paper
• Hepatitis C virus dysregulates glucose homeostasis by a dual mechanism involving induction of PGC1α and dephosphorylation of FoxO1

  2014cites this paper
• Tau protein phosphatases in Alzheimer's disease: the leading role of PP2A.

  2013cites this paper
• Specific Targeting of Caspase-9/PP2A Interaction as Potential New Anti-Cancer Therapy

  2013cites this paper
• Protein phosphatase 2A impairs IFNα‐induced antiviral activity against the hepatitis C virus through the inhibition of STAT1 tyrosine phosphorylation

  2013cites this paper
• Elucidation of the biosynthetic gene cluster and the post-PKS modification mechanism for fostriecin in Streptomyces pulveraceus.

  2013cites this paper
• Regulation of Metabotropic Glutamate Receptor 7 (mGluR7) Internalization and Surface Expression by Ser/Thr Protein Phosphatase 1*

  2013cites this paper
• Suppression of Ser/Thr Phosphatase 4 (PP4C/PPP4C) Mimics a Novel Post-Mitotic Action of Fostriecin, Producing Mitotic Slippage Followed by Tetraploid Cell Death

  2013cites this paper
• Development and applications of highly selective palladium-catalyzed monocoupling reactions of (cyclo)alkenes and 1,3-alkadienes bearing two or three electrophilic sites and bis(enol triflates) with terminal alkynes

  2013cites this paper
• TNF-α Downregulates Inhibitory Neurotransmission through Protein Phosphatase 1-Dependent Trafficking of GABAA Receptors

  2013influential citation
• Viewing serine/threonine protein phosphatases through the eyes of drug designers

  2013cites this paper
• Protein phosphatase 2A activity is required for functional adherent junctions in endothelial cells.

  2013cites this paper
• Cell Cycle and Senescence Suppression of Ser / Thr Phosphatase 4 ( PP 4 C / PPP 4 C ) Mimics a Novel Post-Mitotic Action of Fostriecin , Producing Mitotic Slippage Followed by Tetraploid Cell Death

  2013cites this paper
• Protein Ser/ Thr phosphatases – the ugly ducklings of cell signalling

  2013cites this paper
• Identification of the post-polyketide synthase modification enzymes for fostriecin biosynthesis in Streptomyces pulveraceus.

  2013cites this paper
• Protein phosphatase 1 coordinates CFTR‐dependent airway epithelial HCO3− secretion by reciprocal regulation of apical and basolateral membrane Cl−‐HCO3− exchangers

  2013influential citation
• Bioengineered protein phosphatase 2A

  2013cites this paper
• Osteosarcoma Phenotype Is Inhibited by 3,4-Methylenedioxy-β-nitrostyrene

  2012cites this paper
• Characterization and Activity Determination of the Human Protein Phosphatase 2A Catalytic Subunit α Expressed in Insect Larvae

  2012cites this paper
• Calyculin A Reveals Serine/Threonine Phosphatase Protein Phosphatase 1 as a Regulatory Nodal Point in Canonical Signal Transducer and Activator of Transcription 3 Signaling of Human Microvascular Endothelial Cells

  2012cites this paper
• Acetaldehyde and Epithelial Junctions: Role of Pp2A and Occludin Phosphorylation

  2012cites this paper
• Acetaldehyde disrupts tight junctions in Caco-2 cell monolayers by a protein phosphatase 2A-dependent mechanism.

  2012cites this paper
• Lewy-like aggregation of α-synuclein reduces protein phosphatase 2A activity in vitro and in vivo.

  2012cites this paper
• Chronic receptor-mediated activation of Gi/o proteins alters basal t-tubular and sarcolemmal L-type Ca²⁺ channel activity through phosphatases in heart failure.

  2012influential citation
• 14-3-3ζ Interacts with Stat3 and Regulates Its Constitutive Activation in Multiple Myeloma Cells

  2012cites this paper
• Lenalidomide targets the T-cell co-stimulatory pathway to mediate immune modulation

  2012cites this paper
• MicroRNA-1 and -133 Increase Arrhythmogenesis in Heart Failure by Dissociating Phosphatase Activity from RyR2 Complex

  2011cites this paper
• Regulation of DNA fragmentation: the role of caspases and phosphorylation

  2011cites this paper
• Investigation of phosphatidylinositol 5-phosphate's role in insulin-stimulated glucose uptake in a skeletal muscle cell line

  2011cites this paper
• PP2A targeting by viral proteins: a widespread biological strategy from DNA/RNA tumor viruses to HIV-1.

  2011cites this paper
• Probing mode of action in plant cell cycle by the herbicide endothall, a protein phosphatase inhibitor

  2011cites this paper
• Protein phosphatase 2A mediates resensitization of the neurokinin 1 receptor.

  2011cites this paper
• The anti-tumor antibiotic PD 113,271 binds to microtubule-associated protein 1B (MAP1B)

  2011cites this paper
• The phosphoprotein phosphatase family of Ser/Thr phosphatases as principal targets of naturally occurring toxins

  2011cites this paper
• Protein phosphatase 2A controls the order and dynamics of cell-cycle transitions.

  2011influential citation
• Protein Phosphatase 2A Reactivates FOXO3a through a Dynamic Interplay with 14-3-3 and AKT

  2010cites this paper
• Serine 129 Phosphorylation Reduces the Ability of α-Synuclein to Regulate Tyrosine Hydroxylase and Protein Phosphatase 2A in Vitro and in Vivo

  2010cites this paper
• Protein phosphatase 1 g is responsible for dephosphorylation of histone H 3 at Thr 11 after DNA damage

  2010cites this paper
• Sorting the protein phosphatases: okadaic acid led the way

  2010cites this paper
• Protein phosphatase 1γ is responsible for dephosphorylation of histone H3 at Thr 11 after DNA damage

  2010cites this paper
• PP2A contributes to endothelial death in high glucose: inhibition by benfotiamine.

  2010cites this paper
• Total synthesis of fostriecin: via a regio- and stereoselective polyene hydration, oxidation, and hydroboration sequence.

  2010cites this paper
• LeishBase: Leishmania major structural database.

  2009cites this paper