2008
Structural Analysis of a BAX-BIM SAHB Complex Reveals a Novel BH3 Interaction Site on BAX for Therapeutic Activation of Apoptosis
Gavathiotis E, Suzuki M, Davis M, Pitter K, Bird G, Katz S, Tu H, Kim H, Cheng E, Tjandra N, Walensky L. Structural Analysis of a BAX-BIM SAHB Complex Reveals a Novel BH3 Interaction Site on BAX for Therapeutic Activation of Apoptosis. Blood 2008, 112: 300. DOI: 10.1182/blood.v112.11.300.300.Peer-Reviewed Original ResearchAnti-apoptotic proteinsBax activationCell deathInteraction sitesAlpha-helixBCL-2 domainsBcl-2 family proteinsBcl-2 familyPathologic cell deathBax-mediated apoptosisFirst structural analysisPro-apoptotic proteinsDomain proteinsFamily proteinsMitochondrial translocationProtein interactionsPoint mutagenesisMitochondrial apoptosisStress stimuliBcl-xLConformational changesCell survivalMitochondrial dysfunctionNovel siteDistinct assaysBAX activation is initiated at a novel interaction site
Gavathiotis E, Suzuki M, Davis ML, Pitter K, Bird GH, Katz SG, Tu HC, Kim H, Cheng E, Tjandra N, Walensky LD. BAX activation is initiated at a novel interaction site. Nature 2008, 455: 1076-1081. PMID: 18948948, PMCID: PMC2597110, DOI: 10.1038/nature07396.Peer-Reviewed Original ResearchMeSH KeywordsAmino Acid SequenceAnimalsApoptosisApoptosis Regulatory ProteinsBcl-2-Associated X ProteinBcl-2-Like Protein 11BH3 Interacting Domain Death Agonist ProteinCell LineGene Expression RegulationHumansMembrane ProteinsMiceMutagenesis, Site-DirectedMutationNuclear Magnetic Resonance, BiomolecularProtein BindingProto-Oncogene ProteinsSequence AlignmentConceptsAnti-apoptotic proteinsInteraction sitesBax activationBax-mediated cell deathBCL-2 domainsCell deathBcl-2 familyNovel interaction sitePro-apoptotic proteinsPoint mutagenesisMitochondrial apoptosisBax interactionStress stimuliΑ-helixProteinNew targetsBaxTherapeutic modulationDirect activationActivation siteApoptosisActivationFunctional activitySitesMutagenesis
2007
Pharmacologic Replacement of BIM BH3 Reactivates Apoptosis in Hematologic Cancer and Lymphoproliferative Disease.
LaBelle J, Fisher J, Katz S, Bird G, Lawrence C, Silverstein A, Walensky L. Pharmacologic Replacement of BIM BH3 Reactivates Apoptosis in Hematologic Cancer and Lymphoproliferative Disease. Blood 2007, 110: 524. DOI: 10.1182/blood.v110.11.524.524.Peer-Reviewed Original ResearchAnti-apoptotic proteinsBim-/- miceBcl-2 family protein interactionsBCL-2 domainsBH3-only proteinsRegulation of apoptosisApoptotic signaling pathwaysPro-apoptotic proteinsPromising pharmacologic strategyAnti-apoptotic targetsCellular homeostasisBH3 domainProtein interactionsDeath pathwaysProtein networkCellular survivalSignaling pathwaysApoptotic blockadesCell deathSAHBLymphoma cell linesBH3Apoptosis inductionProteinMitochondrial damage