Linked Life Data

21685396

Source:http://linkedlifedata.com/resource/pubmed/id/21685396

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
31
pubmed:dateCreated
2011-8-1
pubmed:abstractText
Notch is a transmembrane receptor that controls a diverse array of cellular processes including cell proliferation, differentiation, survival, and migration. The cellular outcome of Notch signaling is dependent on extracellular and intracellular signals, but the complexities of its regulation are not well understood. Canonical Notch signaling involves ligand association that triggers sequential and regulated proteolysis of Notch at several sites. Ligand-dependent proteolysis at the S2 site removes the bulk of the extracellular domain of Notch. Subsequent ?-secretase-mediated intramembrane proteolysis of the remaining membrane-tethered Notch fragment at the S3 site produces a nuclear-destined Notch intracellular domain (NICD). Here we show that following ?-secretase cleavage, Notch is proteolyzed at a novel S5 site. We have identified this S5 site to be eight amino acids downstream of the S3 site. Biochemical fractionation and purification resulted in the identification of the S5 site protease as the mitochondrial intermediate peptidase (MIPEP). Expression of the MIPEP-cleaved NICD (?NICD) results in a decrease in cell viability and mitochondria membrane potential. The sequential and regulated proteolysis by ?-secretase and MIPEP suggests a new means by which Notch function can be modulated.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Aug
pubmed:issn
1083-351X
pubmed:author
pubmed:issnType
Electronic
pubmed:day
5
pubmed:volume
286
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
27447-53
pubmed:meshHeading
pubmed:year
2011
pubmed:articleTitle
Gamma-secretase-regulated proteolysis of the Notch receptor by mitochondrial intermediate peptidase.
pubmed:affiliation
Department of Neuroscience, University of Texas Southwestern Medical Center at Dallas, Dallas, Texas 75390, USA.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't, Research Support, N.I.H., Extramural