Linked Life Data

16567805

Source:http://linkedlifedata.com/resource/pubmed/id/16567805

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
22
pubmed:dateCreated
2006-5-29
pubmed:abstractText
IEX-1 (immediate early response gene X-1) is a stress-inducible gene. Its overexpression can suppress or enhance apoptosis dependent on the nature of stress, yet the polypeptide does not possess any of the functional domains that are homologous to those present in well characterized effectors or inhibitors of apoptosis. This study using sequence-targeting mutagenesis reveals a transmembrane-like integrated region of the protein to be critical for both pro-apoptotic and anti-apoptotic functions. Substitution of the key hydrophobic residues with hydrophilic ones within this region impairs the capacity IEX-1 to positively and negatively regulate apoptosis. Mutations at N-linked glycosylation and phosphorylation sites or truncation of the C terminus of IEX-1 also abrogated its potential to promote cell survival. However, distinguished from the transmembrane-like domain, these mutants preserved pro-apoptotic activity of IEX-1 fully. On the contrary, mutation of nuclear localization sequence, despite its importance in apoptosis, did not impede IEX-1-mediated cell survival. Strikingly, all the mutants that lose their anti-apoptotic ability are unable to prevent acute increases in production of intracellular reactive oxygen species (ROS) at the initial onset of apoptosis, whereas those mutants that can sustain anti-death function also control acute ROS production as sufficiently as wild-type IEX-1. These findings suggest a critical role of IEX-1 in regulation of intracellular ROS homeostasis, providing new insight into the mechanism underlying IEX-1-mediated cell survival.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jun
pubmed:issn
0021-9258
pubmed:author
pubmed:issnType
Print
pubmed:day
2
pubmed:volume
281
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
15304-11
pubmed:dateRevised
2010-11-18
pubmed:meshHeading
pubmed-meshheading:16567805-3T3 Cells, pubmed-meshheading:16567805-Animals, pubmed-meshheading:16567805-Apoptosis, pubmed-meshheading:16567805-Apoptosis Regulatory Proteins, pubmed-meshheading:16567805-Biological Transport, Active, pubmed-meshheading:16567805-CHO Cells, pubmed-meshheading:16567805-Caspase 3, pubmed-meshheading:16567805-Caspases, pubmed-meshheading:16567805-Cell Line, pubmed-meshheading:16567805-Cell Survival, pubmed-meshheading:16567805-Cricetinae, pubmed-meshheading:16567805-Enzyme Activation, pubmed-meshheading:16567805-Humans, pubmed-meshheading:16567805-Hydrophobic and Hydrophilic Interactions, pubmed-meshheading:16567805-Membrane Proteins, pubmed-meshheading:16567805-Mice, pubmed-meshheading:16567805-Mitochondria, pubmed-meshheading:16567805-Mutagenesis, Site-Directed, pubmed-meshheading:16567805-Nuclear Localization Signals, pubmed-meshheading:16567805-Protein Structure, Tertiary, pubmed-meshheading:16567805-Reactive Oxygen Species, pubmed-meshheading:16567805-Recombinant Proteins
pubmed:year
2006
pubmed:articleTitle
Distinct domains for anti- and pro-apoptotic activities of IEX-1.
pubmed:affiliation
Wellman Center of Photomedicine, Massachusetts General Hospital, Boston, Massachusetts 02114, USA.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't, Research Support, N.I.H., Extramural