Linked Life Data

21324892

Source:http://linkedlifedata.com/resource/pubmed/id/21324892

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
21
pubmed:dateCreated
2011-5-23
pubmed:abstractText
The expression levels of caspase-8 inhibitory c-FLIP proteins play an important role in regulating death receptor-mediated apoptosis, as their concentration at the moment when the death-inducing signaling complex (DISC) is formed determines the outcome of the DISC signal. Experimental studies have shown that c-FLIP proteins are subject to dynamic turnover and that their stability and expression levels can be rapidly altered. Even though the influence of c-FLIP on the apoptotic behavior of a single cell has been captured in mathematical simulation studies, the effect of c-FLIP turnover and stability has not been investigated. In this study, a mathematical model of apoptosis was developed to analyze how the dynamic turnover and stability of the c-FLIP isoforms regulate apoptotic signaling for both individual cells and cell populations. Intercellular parameter and concentration distributions were used to describe the behavior of cell populations. Monte-Carlo simulations of cell populations showed that c-FLIP turnover is a key determinant of death receptor responses. The fact that the developed model simulates the state of whole cell populations makes it possible to validate it by comparison with empirical data. The proposed modeling approach can be used to further determine limiting factors in the DISC signaling process.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
May
pubmed:issn
1083-351X
pubmed:author
pubmed:issnType
Electronic
pubmed:day
27
pubmed:volume
286
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
18375-82
pubmed:meshHeading
pubmed:year
2011
pubmed:articleTitle
Modeling reveals that dynamic regulation of c-FLIP levels determines cell-to-cell distribution of CD95-mediated apoptosis.
pubmed:affiliation
Department of Information Technologies, Åbo Akademi University, FI-20500 Turku, Finland.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't