Search results for "kinases"

showing 10 items of 929 documents

The E3 Ubiquitin Ligase MID1 Catalyzes Ubiquitination and Cleavage of Fu

2014

Sonic Hedgehog (SHH)-GLI signalling plays an important role during embryogenesis and in tumorigenesis. The survival and growth of several types of cancer depend on autonomously activated SHH-GLI signalling. A protein complex containing the ubiquitin-ligase MID1 and protein phosphatase 2A (PP2A) regulates the nuclear localization and transcriptional activity of GLI3, a transcriptional effector molecule of SHH, in cancer cell lines with autonomously activated SHH signalling. However, the exact molecular mechanisms that mediate the interaction between MID1 and GLI3 remained unknown. Here, we show that MID1 catalyses the ubiquitination and proteasomal cleavage of the GLI3-regulator Fu. Our data…

metabolism [Microtubule Proteins]Ubiquitin-conjugating enzymeBiochemistrymetabolism [Protein Serine-Threonine Kinases]Ubiquitinmetabolism [Transcription Factors]Nuclear proteinSonic hedgehogbiologymetabolism [Protein-Serine-Threonine Kinases]Nuclear Proteinsrespiratory systemProtein-Serine-Threonine KinasesUbiquitin ligaseGene Expression Regulation NeoplasticGLI3 protein humanBiochemistryddc:540embryonic structuresMicrotubule Proteinsmetabolism [Hedgehog Proteins]Function and Dysfunction of the Nervous Systemmetabolism [Nuclear Proteins]Signal Transductionmetabolism [Kruppel-Like Transcription Factors]Proteasome Endopeptidase Complexanimal structuresSTK36 protein humanUbiquitin-Protein LigasesKruppel-Like Transcription FactorsNerve Tissue ProteinsProtein Serine-Threonine Kinaseschemistry [Ubiquitin-Protein Ligases]CatalysisZinc Finger Protein Gli3Cell Line TumorGLI3HumansHedgehog Proteinsmetabolism [Proteasome Endopeptidase Complex]metabolism [Cell Nucleus]Molecular Biologychemistry [Lysine]DNA PrimersCell Nucleusmetabolism [Nerve Tissue Proteins]UbiquitinLysineUbiquitinationCell BiologyProtein phosphatase 2chemistry [Ubiquitin]Proteasomebiology.proteinSHH protein humanhuman activitiesMid1 protein humanHeLa CellsTranscription FactorsJournal of Biological Chemistry
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Targeting GSK3 and Associated Signaling Pathways Involved in Cancer

2020

Glycogen synthase kinase 3 (GSK-3) is a serine/threonine (S/T) protein kinase. Although GSK-3 originally was identified to have functions in regulation of glycogen synthase, it was subsequently determined to have roles in multiple normal biochemical processes as well as various disease conditions. GSK-3 is sometimes referred to as a moonlighting protein due to the multiple substrates and processes which it controls. Frequently, when GSK-3 phosphorylates proteins, they are targeted for degradation. GSK-3 is often considered a component of the PI3K/PTEN/AKT/GSK-3/mTORC1 pathway as GSK-3 is frequently phosphorylated by AKT which regulates its inactivation. AKT is often active in human cancer a…

natural productnatural productsmTORC1Reviewmacromolecular substancesProtein Serine-Threonine KinasesGlycogen Synthase Kinase 3GSK-3NeoplasmsHumansPhosphorylationProtein kinase AGlycogen synthaselcsh:QH301-705.5Protein kinase BWnt Signaling PathwayPI3K/AKT/mTOR pathwayGSK-3drug resistancenaturalproductsbiologyChemistryWnt signaling pathwayGeneral Medicinetargeted therapyCell biologylcsh:Biology (General)biology.proteinSignal transductionProto-Oncogene Proteins c-akt
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Structural Manipulations of Marine Natural Products Inspire a New Library of 3-Amino-1,2,4-Triazine PDK Inhibitors Endowed with Antitumor Activity in…

2023

Pancreatic ductal adenocarcinoma (PDAC) is one of the main aggressive types of cancer, characterized by late prognosis and drug resistance. Among the main factors sustaining PDAC progression, the alteration of cell metabolism has emerged to have a key role in PDAC cell proliferation, invasion, and resistance to standard chemotherapeutic agents. Taking into account all these factors and the urgency in evaluating novel options to treat PDAC, in the present work we reported the synthesis of a new series of indolyl-7-azaindolyl triazine compounds inspired by marine bis-indolyl alkaloids. We first assessed the ability of the new triazine compounds to inhibit the enzymatic activity of pyruvate de…

nortopsentin analoguespancreatic ductal adenocarcinoma (PDAC); nortopsentin analogues; antitumor activity; pyruvate dehydrogenase kinases (PDKs); cytotoxic activity; metabolic alterations; ligand-based homology modeling; KRASDrug Discoveryligand-based homology modelingKRASPharmaceutical Scienceantitumor activitymetabolic alterationspancreatic ductal adenocarcinoma (PDAC)Pharmacology Toxicology and Pharmaceutics (miscellaneous)cytotoxic activitypyruvate dehydrogenase kinases (PDKs)
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Activation of the p38MAPK cascade is associated with upregulation of TNF alpha receptors in the spinal motor neurons of mouse models of familial ALS.

2005

Phosphorylated p38 mitogen-activated protein kinase (p38MAPK), but not activated c-jun-N-terminal kinase (JNK), increases in the motor neurons of transgenic mice overexpressing ALS-linked SOD1 mutants at different stages of the disease. This effect is associated with a selective increase of phosphorylated MKK3-6, MKK4 and ASK1 and a concomitant upregulation of the TNFalpha receptors (TNFR1 and TNFR2), but not IL1beta and Fas receptors. Activation of both p38 MAPK and JNK occurs in the activated microglial cells of SOD1 mutant mice at the advanced stage of the disease; however, this effect is not accompanied by the concomitant activation of the upstream kinases ASK1 and MKK3,4,6, while both …

p38 mitogen-activated protein kinasesMAP Kinase Kinase 3Mice TransgenicMAP Kinase Kinase 6BiologyMAP Kinase Kinase Kinase 5p38 Mitogen-Activated Protein KinasesReceptors Tumor Necrosis FactorCellular and Molecular NeuroscienceMiceSuperoxide Dismutase-1Downregulation and upregulationAnimalsHumansASK1RNA Messengerfas ReceptorPhosphorylationReceptorProtein kinase AMolecular BiologyP38MAPK cascadeMotor NeuronsKinaseSuperoxide DismutaseTumor Necrosis Factor-alphaAmyotrophic Lateral SclerosisJNK Mitogen-Activated Protein KinasesReceptors Interleukin-1Cell BiologyCell biologyEnzyme ActivationMice Inbred C57BLDisease Models AnimalTumor Necrosis Factor Decoy ReceptorsSpinal CordReceptors Tumor Necrosis Factor Type IDisease ProgressionTumor necrosis factor alphaSignal TransductionMolecular and cellular neurosciences
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Protein Phosphorylation by Peroxisome Proliferators: Species-specific Stimulation of Protein Kinases and Its Role in PP-induced Transcriptional Activ…

1996

p38 mitogen-activated protein kinasesMicrobodiesGene Expression Regulation EnzymologicGeneral Biochemistry Genetics and Molecular BiologyMAP2K7Retinoblastoma-like protein 1History and Philosophy of ScienceAnimalsHumansProtein phosphorylationClofibrateRNA MessengerAcetyl-CoA C-AcetyltransferaseProtein kinase ACells CulturedProtein Kinase CHypolipidemic AgentsbiologyChemistryKinaseGeneral NeuroscienceGRB10Autophagy-related protein 13PhosphoproteinsStaurosporineRats Inbred F344RatsCell biologybiology.proteinProtein KinasesAnnals of the New York Academy of Sciences
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Endoderm development requires centrioles to restrain p53-mediated apoptosis in the absence of ERK activity

2021

Centrioles comprise the heart of centrosomes, microtubule-organizing centers. To study the function of centrioles in lung and gut development, we genetically disrupted centrioles throughout the mouse endoderm. Surprisingly, removing centrioles from the endoderm did not disrupt intestinal growth or development but blocked lung branching. In the lung, acentriolar SOX2-expressing airway epithelial cells apoptosed. Loss of centrioles activated p53, and removing p53 restored survival of SOX2-expressing cells, lung branching, and mouse viability. To investigate how endodermal p53 activation specifically killed acentriolar SOX2-expressing cells, we assessed ERK, a prosurvival cue. ERK was active t…

p53Cell SurvivalApoptosisInbred C57BLMedical and Health SciencesArticleGeneral Biochemistry Genetics and Molecular BiologyMiceMorphogenesis2.1 Biological and endogenous factorsAnimalscentrioleintestine developmentAetiologyExtracellular Signal-Regulated MAP KinasesendodermLungMolecular BiologyCentriolesSOXB1 Transcription FactorsStem CellsEndodermapoptosisEpithelial CellsCell BiologyBiological SciencesIntestinesMice Inbred C57BLlung branchingERKembryonic structuresTumor Suppressor Protein p53Microtubule-Associated ProteinsDevelopmental BiologyDevelopmental Cell
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Activation of NF-kappaB and IL-8 by yersinia enterocolitica invasin protein is conferred by engagement of rac1 and MAP kinase cascades.

2003

International audience; Yersinia enterocolitica triggers activation of the nuclear factor (NF)-kappaB and production of the proinflammatory chemokine interleukin (IL)-8 in intestinal epithelial cells. This activation is due to adhesion of the bacteria via their outer membrane protein invasin to the host cells. Using Clostridium difficile toxins that specifically inactivate small GTPases, and transfection of inhibitory proteins of the Rho-GTPases, we demonstrate that Rac1, but not Cdc42 or Rho, is required for activation of NF-kappaB by invasin. Invasin activated the mitogen activated protein kinases (MAPK) p38 and c-Jun N-terminal protein kinase (JNK) but not extracellular signal regulated …

rac1 GTP-Binding ProteinMAP Kinase Kinase 4MAP Kinase Signaling SystemRNA Stability[SDV]Life Sciences [q-bio]ImmunologyMitogen-activated protein kinase kinasep38 Mitogen-Activated Protein KinasesMicrobiologyBacterial AdhesionMAP2K703 medical and health sciencesBacterial ProteinsVirologyHumansASK1RNA Messengerc-RafAdhesins Bacterialcdc42 GTP-Binding ProteinrhoB GTP-Binding ProteinYersinia enterocolitica030304 developmental biologyMitogen-Activated Protein Kinase Kinases0303 health sciencesbiologyMAP kinase kinase kinase030306 microbiologyInterleukin-8Cyclin-dependent kinase 2JNK Mitogen-Activated Protein KinasesNF-kappa BProtein kinase RMolecular biologyCell biologybiology.proteinCyclin-dependent kinase 9Mitogen-Activated Protein KinasesrhoA GTP-Binding ProteinHeLa CellsSignal Transduction
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Aplidin® induces JNK-dependent apoptosis in human breast cancer cells via alteration of glutathione homeostasis, Rac1 GTPase activation, and MKP-1 ph…

2006

Aplidin® is an antitumor agent in phase II clinical trials that induces apoptosis through the sustained activation of Jun N-terminal kinase (JNK). We report that Aplidin® alters glutathione homeostasis increasing the ratio of oxidized to reduced forms (GSSG/GSH). Aplidin® generates reactive oxygen species and disrupts the mitochondrial membrane potential. Exogenous GSH inhibits these effects and also JNK activation and cell death. We found two mechanisms by which Aplidin® activates JNK: rapid activation of Rac1 small GTPase and downregulation of MKP-1 phosphatase. Rac1 activation was diminished by GSH and enhanced by L-buthionine (SR)-sulfoximine, which inhibits GSH synthesis. Downregulatio…

rac1 GTP-Binding ProteinProgrammed cell deathSmall interfering RNAGlutathione reductaseDown-RegulationAntineoplastic AgentsApoptosisBreast NeoplasmsCell Cycle ProteinsBiologyPeptides CyclicImmediate-Early ProteinsMembrane Potentialschemistry.chemical_compoundMiceDownregulation and upregulationDepsipeptidesProtein Phosphatase 1Phosphoprotein PhosphatasesAnimalsHomeostasisHumansMolecular Biologychemistry.chemical_classificationReactive oxygen speciesGlutathione PeroxidaseGlutathione DisulfideJNK Mitogen-Activated Protein KinasesProtein phosphatase 1Dual Specificity Phosphatase 1Cell BiologyGlutathioneCell biologyEnzyme ActivationOxidative StressGlutathione ReductasechemistryMitochondrial MembranesGlutathione disulfideCalciumProtein Tyrosine PhosphatasesReactive Oxygen SpeciesCopperHeLa CellsCell Death and Differentiation
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Rac1 and PAK1 are upstream of IKK-ε and TBK-1 in the viral activation of interferon regulatory factor-3

2004

The anti-viral type I interferon (IFN) response is initiated by the immediate induction of IFN beta, which is mainly controlled by the IFN-regulatory factor-3 (IRF-3). The signaling pathways mediating viral IRF-3 activation are only poorly defined. We show that the Rho GTPase Rac1 is activated upon virus infection and controls IRF-3 phosphorylation and activity. Inhibition of Rac1 leads to reduced IFN beta promoter activity and to enhanced virus production. As a downstream mediator of Rac signaling towards IRF-3, we have identified the kinase p21-activated kinase (PAK1). Furthermore, both Rac1 and PAK1 regulate the recently described IRF-3 activators, I kappa B kinase- and TANK-binding kina…

rac1 GTP-Binding ProteinTranscription GeneticBiophysicsIκB kinaseProtein Serine-Threonine KinasesSignal transductionBiologyVirus ReplicationBiochemistryCell LineDogsPAK1Structural BiologyInterferonGeneticsmedicineAnimalsHumansPhosphorylationPromoter Regions Geneticp21-activated kinasesMolecular BiologyRNA Double-StrandedKinaseRho GTPaseI-Kappa-B KinaseNuclear ProteinsInterferon-betaCell BiologyCREB-Binding ProteinI-kappa B KinaseDNA-Binding ProteinsEnzyme Activationp21-Activated KinasesInfluenza A virusViral infectionAnti-viral responseTrans-ActivatorsCancer researchInterferon Regulatory Factor-3Transcription factorSignal transductionDimerizationTranscription FactorsInterferon regulatory factorsmedicine.drugFEBS Letters
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Rho GTPases are over-expressed in human tumors.

1999

Small GTPases of the Rho family are involved in the regulation of a variety of cellular processes, such as the organization of the microfilamental network, cell-cell contact and malignant transformation. To address the question of whether Rho proteins are involved in carcinogenesis in man, we compared their expression in tumors from colon, breast and lung with that of the corresponding normal tissue originating from the same patient. As shown by Rho-specific 32P-ADP-ribosylation, as well as Western-blot analysis, the amount of RhoA protein was largely increased in all 3 types of tumors tested. The most dramatic differences in the expression of Rho GTPases were observed in breast tissue. All…

rho GTP-Binding ProteinsCancer ResearchPathologymedicine.medical_specialtyRHOALung NeoplasmsColonBreast NeoplasmsCell Cycle ProteinsGTPaseCDC42medicine.disease_causeMalignant transformationGTP PhosphohydrolasesGTP-Binding ProteinsmedicineHumansrho-Specific Guanine Nucleotide Dissociation InhibitorsBreastcdc42 GTP-Binding ProteinrhoB GTP-Binding ProteinLungGuanine Nucleotide Dissociation InhibitorsMitogen-Activated Protein Kinase 1Adenosine Diphosphate RibosebiologyCancerMembrane Proteinsmedicine.diseaseImmunohistochemistryrac GTP-Binding ProteinsOncologyrhoC GTP-Binding ProteinCalcium-Calmodulin-Dependent Protein KinasesColonic Neoplasmsbiology.proteinCancer researchImmunohistochemistryCarcinogenesisrhoA GTP-Binding ProteinRhoC GTP-Binding ProteinInternational journal of cancer
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