Linked Life Data

20392206

Source:http://linkedlifedata.com/resource/pubmed/id/20392206

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
5
pubmed:dateCreated
2010-4-15
pubmed:abstractText
The truncated C-terminal portion of Bid (tBid) is an important intermediate in ligand-induced apoptosis. tBid has been shown to be sensitive to proteasomal inhibitors and downregulated by activation of the epidermal growth factor (EGF) pathway. Here, we provide evidence that tBid is a substrate of the ubiquitin ligase Itch, which can specifically interact with and ubiquitinate tBid, but not intact Bid. Consistently, overexpression of Itch increases cell survival and inhibits caspase 3 activity, whereas downregulation of Itch by RNA interference has the opposite effect, increasing cell death and apoptosis. Treatment with EGF increases Itch phosphorylation and activity, and Itch expression is important for the ability of EGF to increase cell survival after tumour necrosis factor-related apoptosis-inducing ligand treatment. Our findings identify Itch as a key molecule between EGF signalling and resistance to apoptosis through downregulation of tBid, providing further details on how EGF receptor and proteasome inhibitors can contribute to the induction of apoptosis and the treatment of cancer.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Mar
pubmed:issn
1742-4658
pubmed:author
pubmed:issnType
Electronic
pubmed:volume
277
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1319-30
pubmed:meshHeading
pubmed:year
2010
pubmed:articleTitle
The ubiquitin ligase Itch mediates the antiapoptotic activity of epidermal growth factor by promoting the ubiquitylation and degradation of the truncated C-terminal portion of Bid.
pubmed:affiliation
Département de sciences biologiques, Université de Montréal, Montréal, Québec, Canada.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't