Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2
pubmed:dateCreated
2011-1-10
pubmed:abstractText
Accumulation of misfolded proteins in the endoplasmic reticulum (ER) causes ER stress and activates inositol-requiring protein-1 (IRE1), among other ER-associated signaling proteins of the unfolded protein response (UPR) in mammalian cells. IRE1 signaling becomes attenuated under prolonged ER stress. The mechanisms by which this occurs are not well understood. An ER resident protein, Bax inhibitor-1 (BI-1), interacts with IRE1 and directly inhibits IRE1 activity. However, little is known about regulation of the BI-1 protein. We show here that bifunctional apoptosis regulator (BAR) functions as an ER-associated RING-type E3 ligase, interacts with BI-1, and promotes proteasomal degradation of BI-1. Overexpression of BAR reduced BI-1 protein levels in a RING-dependent manner. Conversely, knockdown of endogenous BAR increased BI-1 protein levels and enhanced inhibition of IRE1 signaling during ER stress. We also found that the levels of endogenous BAR were reduced under prolonged ER stress. Our findings suggest that post-translational regulation of the BI-1 protein by E3 ligase BAR contributes to the dynamic control of IRE1 signaling during ER stress.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jan
pubmed:issn
1083-351X
pubmed:author
pubmed:issnType
Electronic
pubmed:day
14
pubmed:volume
286
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1453-63
pubmed:dateRevised
2011-10-14
pubmed:meshHeading
pubmed-meshheading:21068390-Adaptor Proteins, Signal Transducing, pubmed-meshheading:21068390-Apoptosis Regulatory Proteins, pubmed-meshheading:21068390-Endoplasmic Reticulum, pubmed-meshheading:21068390-Endoribonucleases, pubmed-meshheading:21068390-HEK293 Cells, pubmed-meshheading:21068390-HeLa Cells, pubmed-meshheading:21068390-Humans, pubmed-meshheading:21068390-Membrane Proteins, pubmed-meshheading:21068390-Proteasome Endopeptidase Complex, pubmed-meshheading:21068390-Protein Processing, Post-Translational, pubmed-meshheading:21068390-Protein-Serine-Threonine Kinases, pubmed-meshheading:21068390-Signal Transduction, pubmed-meshheading:21068390-Stress, Physiological, pubmed-meshheading:21068390-Transfection, pubmed-meshheading:21068390-Ubiquitin-Protein Ligases, pubmed-meshheading:21068390-Ubiquitination
pubmed:year
2011
pubmed:articleTitle
Bifunctional apoptosis regulator (BAR), an endoplasmic reticulum (ER)-associated E3 ubiquitin ligase, modulates BI-1 protein stability and function in ER Stress.
pubmed:affiliation
Sanford-Burnham Medical Research Institute, La Jolla, California 92037, USA.
pubmed:publicationType
Journal Article, In Vitro, Research Support, Non-U.S. Gov't, Research Support, N.I.H., Extramural