0000000000540155

AUTHOR

A Murat Kaya

showing 2 related works from this author

BAG3 mediates chaperone-based aggresome-targeting and selective autophagy of misfolded proteins.

2010

Increasing evidence indicates the existence of selective autophagy pathways, but the manner in which substrates are recognized and targeted to the autophagy system is poorly understood. One strategy is transport of a particular substrate to the aggresome, a perinuclear compartment with high autophagic activity. In this paper, we identify a new cellular pathway that uses the specificity of heat-shock protein 70 (Hsp70) to misfolded proteins as the basis for aggresome-targeting and autophagic degradation. This pathway is regulated by the stress-induced co-chaperone Bcl-2-associated athanogene 3 (BAG3), which interacts with the microtubule-motor dynein and selectively directs Hsp70 substrates …

Protein FoldingRecombinant Fusion ProteinsDyneinGreen Fluorescent ProteinsAggrephagyMice TransgenicBAG3BiochemistryMiceJUNQ and IPODChlorocebus aethiopsGeneticsAutophagyAnimalsHumansPoint MutationHSP70 Heat-Shock ProteinsMolecular BiologyAdaptor Proteins Signal TransducingSequence DeletionInclusion BodiesMotor NeuronsbiologySuperoxide DismutaseAutophagyScientific ReportsDyneinsTransport proteinCell biologyProtein TransportAggresomeHEK293 CellsSpinal CordChaperone (protein)COS Cellsbiology.proteinApoptosis Regulatory ProteinsProteasome InhibitorsEMBO reports
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Protein quality control during aging involves recruitment of the macroautophagy pathway by BAG3.

2009

The Hsc/Hsp70 co-chaperones of the BAG (Bcl-2-associated athanogene) protein family are modulators of protein quality control. We examined the specific roles of BAG1 and BAG3 in protein degradation during the aging process. We show that BAG1 and BAG3 regulate proteasomal and macroautophagic pathways, respectively, for the degradation of polyubiquitinated proteins. Moreover, using models of cellular aging, we find that a switch from BAG1 to BAG3 determines that aged cells use more intensively the macroautophagic system for turnover of polyubiquitinated proteins. This increased macroautophagic flux is regulated by BAG3 in concert with the ubiquitin-binding protein p62/SQSTM1. The BAG3/BAG1 ra…

BAG domainProteasome Endopeptidase ComplexProtein familyProtein degradationBAG3ubiquitinationGeneral Biochemistry Genetics and Molecular BiologyBAG1ArticleRats Sprague-DawleyMiceUbiquitinMicroscopy Electron TransmissionAutophagyAnimalsHumansSQSTM1Molecular BiologyCellular SenescenceAdaptor Proteins Signal TransducingBAG1General Immunology and MicrobiologybiologyGeneral Neurosciencep62ImmunohistochemistryCell biologyRatsDNA-Binding ProteinsproteasomeProteasomeBiochemistrybiology.proteinApoptosis Regulatory ProteinsFlux (metabolism)Transcription FactorsThe EMBO journal
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