Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
9
pubmed:dateCreated
2009-2-23
pubmed:abstractText
Aggregation of mutated proteins is a hallmark of many neurodegenerative disorders, including Huntington disease. We previously reported that overexpression of the HspB8.Bag3 chaperone complex suppresses mutated huntingtin aggregation via autophagy. Classically, HspB proteins are thought to act as ATP-independent molecular chaperones that can bind unfolded proteins and facilitate their processing via the help of ATP-dependent chaperones such as the Hsp70 machine, in which Bag3 may act as a molecular link between HspB, Hsp70, and the ubiquitin ligases. However, here we show that HspB8 and Bag3 act in a non-canonical manner unrelated to the classical chaperone model. Rather, HspB8 and Bag3 induce the phosphorylation of the alpha-subunit of the translation initiator factor eIF2, which in turn causes a translational shut-down and stimulates autophagy. This function of HspB8.Bag3 does not require Hsp70 and also targets fully folded substrates. HspB8.Bag3 activity was independent of the endoplasmic reticulum (ER) stress kinase PERK, demonstrating that its action is unrelated to ER stress and suggesting that it activates stress-mediated translational arrest and autophagy through a novel pathway.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
http://linkedlifedata.com/resource/pubmed/chemical/Adaptor Proteins, Signal Transducing, http://linkedlifedata.com/resource/pubmed/chemical/Atg5 protein, mouse, http://linkedlifedata.com/resource/pubmed/chemical/BAG3 protein, human, http://linkedlifedata.com/resource/pubmed/chemical/Eif2ak4 protein, mouse, http://linkedlifedata.com/resource/pubmed/chemical/Eukaryotic Initiation Factor-2, http://linkedlifedata.com/resource/pubmed/chemical/HD protein, human, http://linkedlifedata.com/resource/pubmed/chemical/HSPB8 protein, human, http://linkedlifedata.com/resource/pubmed/chemical/Heat-Shock Proteins, http://linkedlifedata.com/resource/pubmed/chemical/Microtubule-Associated Proteins, http://linkedlifedata.com/resource/pubmed/chemical/Molecular Chaperones, http://linkedlifedata.com/resource/pubmed/chemical/Nerve Tissue Proteins, http://linkedlifedata.com/resource/pubmed/chemical/Nuclear Proteins, http://linkedlifedata.com/resource/pubmed/chemical/PERK kinase, http://linkedlifedata.com/resource/pubmed/chemical/Protein-Serine-Threonine Kinases, http://linkedlifedata.com/resource/pubmed/chemical/Recombinant Proteins, http://linkedlifedata.com/resource/pubmed/chemical/eIF-2 Kinase
pubmed:status
MEDLINE
pubmed:month
Feb
pubmed:issn
0021-9258
pubmed:author
pubmed:issnType
Print
pubmed:day
27
pubmed:volume
284
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
5523-32
pubmed:dateRevised
2009-11-19
pubmed:meshHeading
pubmed-meshheading:19114712-Adaptor Proteins, Signal Transducing, pubmed-meshheading:19114712-Animals, pubmed-meshheading:19114712-Autophagy, pubmed-meshheading:19114712-Cells, Cultured, pubmed-meshheading:19114712-Embryo, Mammalian, pubmed-meshheading:19114712-Eukaryotic Initiation Factor-2, pubmed-meshheading:19114712-Fibroblasts, pubmed-meshheading:19114712-Heat-Shock Proteins, pubmed-meshheading:19114712-Humans, pubmed-meshheading:19114712-Mice, pubmed-meshheading:19114712-Mice, Knockout, pubmed-meshheading:19114712-Microtubule-Associated Proteins, pubmed-meshheading:19114712-Molecular Chaperones, pubmed-meshheading:19114712-Nerve Tissue Proteins, pubmed-meshheading:19114712-Nuclear Proteins, pubmed-meshheading:19114712-Phosphorylation, pubmed-meshheading:19114712-Protein Biosynthesis, pubmed-meshheading:19114712-Protein-Serine-Threonine Kinases, pubmed-meshheading:19114712-RNA Stability, pubmed-meshheading:19114712-Recombinant Proteins, pubmed-meshheading:19114712-Trinucleotide Repeats, pubmed-meshheading:19114712-eIF-2 Kinase
pubmed:year
2009
pubmed:articleTitle
HspB8 participates in protein quality control by a non-chaperone-like mechanism that requires eIF2{alpha} phosphorylation.
pubmed:affiliation
Department of Radiation and Stress Cell Biology, University Medical Center Groningen, A. Deusinglaan 1, 9713 AV Groningen, The Netherlands. s.carra@med.umcg.nl
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't