Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2
pubmed:dateCreated
2007-7-27
pubmed:abstractText
Two major protein degradation systems exist in cells, the ubiquitin proteasome system and the autophagy machinery. Here, we investigated the functional relationship of the two systems and the underlying mechanisms. Proteasome inhibition activated autophagy, suggesting that the two are functionally coupled. Autophagy played a compensatory role as suppression of autophagy promoted the accumulation of polyubiquitinated protein aggregates. Autophagy was likely activated in response to endoplasmic reticulum stress caused by misfolded proteins during proteasome inhibition. Suppression of a major unfolded protein response pathway mediated by IRE1 by either gene deletion or RNA interference dramatically suppressed the activation of autophagy by proteasome inhibitors. Interestingly, c-Jun NH(2)-terminal kinase (JNK) but not XBP-1, both of which are the known downstream targets of IRE1, seemed to participate in autophagy induction by proteasome inhibitors. Finally, proteasome inhibitor-induced autophagy was important for controlling endoplasmic reticulum stress and reducing cell death in cancer cells. Our studies thus provide a mechanistic view and elucidate the functional significance of the link between the two protein degradation systems.
pubmed:grant
pubmed:commentsCorrections
http://linkedlifedata.com/resource/pubmed/commentcorrection/17620365-10650002, http://linkedlifedata.com/resource/pubmed/commentcorrection/17620365-11060023, http://linkedlifedata.com/resource/pubmed/commentcorrection/17620365-11062132, http://linkedlifedata.com/resource/pubmed/commentcorrection/17620365-11375494, http://linkedlifedata.com/resource/pubmed/commentcorrection/17620365-11577074, http://linkedlifedata.com/resource/pubmed/commentcorrection/17620365-11779464, http://linkedlifedata.com/resource/pubmed/commentcorrection/17620365-11780124, http://linkedlifedata.com/resource/pubmed/commentcorrection/17620365-12050113, http://linkedlifedata.com/resource/pubmed/commentcorrection/17620365-12142265, http://linkedlifedata.com/resource/pubmed/commentcorrection/17620365-12417557, http://linkedlifedata.com/resource/pubmed/commentcorrection/17620365-12902539, http://linkedlifedata.com/resource/pubmed/commentcorrection/17620365-14536056, http://linkedlifedata.com/resource/pubmed/commentcorrection/17620365-14560952, http://linkedlifedata.com/resource/pubmed/commentcorrection/17620365-14765132, http://linkedlifedata.com/resource/pubmed/commentcorrection/17620365-15031729, http://linkedlifedata.com/resource/pubmed/commentcorrection/17620365-15068787, http://linkedlifedata.com/resource/pubmed/commentcorrection/17620365-15144949, http://linkedlifedata.com/resource/pubmed/commentcorrection/17620365-15146184, http://linkedlifedata.com/resource/pubmed/commentcorrection/17620365-15209383, http://linkedlifedata.com/resource/pubmed/commentcorrection/17620365-15325579, http://linkedlifedata.com/resource/pubmed/commentcorrection/17620365-15368445, http://linkedlifedata.com/resource/pubmed/commentcorrection/17620365-15509775, http://linkedlifedata.com/resource/pubmed/commentcorrection/17620365-15525940, http://linkedlifedata.com/resource/pubmed/commentcorrection/17620365-15528435, http://linkedlifedata.com/resource/pubmed/commentcorrection/17620365-15530777, http://linkedlifedata.com/resource/pubmed/commentcorrection/17620365-15538170, http://linkedlifedata.com/resource/pubmed/commentcorrection/17620365-15657430, http://linkedlifedata.com/resource/pubmed/commentcorrection/17620365-15757910, http://linkedlifedata.com/resource/pubmed/commentcorrection/17620365-15928708, http://linkedlifedata.com/resource/pubmed/commentcorrection/17620365-15952902, http://linkedlifedata.com/resource/pubmed/commentcorrection/17620365-16056268, http://linkedlifedata.com/resource/pubmed/commentcorrection/17620365-16183649, http://linkedlifedata.com/resource/pubmed/commentcorrection/17620365-16267277, http://linkedlifedata.com/resource/pubmed/commentcorrection/17620365-16357160, http://linkedlifedata.com/resource/pubmed/commentcorrection/17620365-16365039, http://linkedlifedata.com/resource/pubmed/commentcorrection/17620365-16522639, http://linkedlifedata.com/resource/pubmed/commentcorrection/17620365-16565503, http://linkedlifedata.com/resource/pubmed/commentcorrection/17620365-16625204, http://linkedlifedata.com/resource/pubmed/commentcorrection/17620365-16625205, http://linkedlifedata.com/resource/pubmed/commentcorrection/17620365-16794605, http://linkedlifedata.com/resource/pubmed/commentcorrection/17620365-16843265, http://linkedlifedata.com/resource/pubmed/commentcorrection/17620365-16901900, http://linkedlifedata.com/resource/pubmed/commentcorrection/17620365-17030611, http://linkedlifedata.com/resource/pubmed/commentcorrection/17620365-17132049, http://linkedlifedata.com/resource/pubmed/commentcorrection/17620365-17135238, http://linkedlifedata.com/resource/pubmed/commentcorrection/17620365-17244528, http://linkedlifedata.com/resource/pubmed/commentcorrection/17620365-6952238, http://linkedlifedata.com/resource/pubmed/commentcorrection/17620365-7750517, http://linkedlifedata.com/resource/pubmed/commentcorrection/17620365-9759494
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
AIM
pubmed:chemical
http://linkedlifedata.com/resource/pubmed/chemical/BAX protein, human, http://linkedlifedata.com/resource/pubmed/chemical/Cysteine Proteinase Inhibitors, http://linkedlifedata.com/resource/pubmed/chemical/ERN2 protein, human, http://linkedlifedata.com/resource/pubmed/chemical/Endoribonucleases, http://linkedlifedata.com/resource/pubmed/chemical/Green Fluorescent Proteins, http://linkedlifedata.com/resource/pubmed/chemical/Leupeptins, http://linkedlifedata.com/resource/pubmed/chemical/Membrane Proteins, http://linkedlifedata.com/resource/pubmed/chemical/Microtubule-Associated Proteins, http://linkedlifedata.com/resource/pubmed/chemical/Proteasome Endopeptidase Complex, http://linkedlifedata.com/resource/pubmed/chemical/Protein-Serine-Threonine Kinases, http://linkedlifedata.com/resource/pubmed/chemical/Recombinant Fusion Proteins, http://linkedlifedata.com/resource/pubmed/chemical/Ubiquitin, http://linkedlifedata.com/resource/pubmed/chemical/bcl-2-Associated X Protein, http://linkedlifedata.com/resource/pubmed/chemical/benzyloxycarbonylleucyl-leucyl-leuci..., http://linkedlifedata.com/resource/pubmed/chemical/light chain 3, human
pubmed:status
MEDLINE
pubmed:month
Aug
pubmed:issn
0002-9440
pubmed:author
pubmed:issnType
Print
pubmed:volume
171
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
513-24
pubmed:dateRevised
2009-11-18
pubmed:meshHeading
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