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c-FLIPL enhances anti-apoptotic Akt functions by modulation of Gsk3β activity.
- Source :
- Cell Death & Differentiation; Dec2010, Vol. 17 Issue 12, p1908-1916, 9p, 1 Black and White Photograph, 2 Diagrams, 3 Graphs
- Publication Year :
- 2010
-
Abstract
- Akt is a serine-threonine kinase that has an important role in transducing survival signals. Akt also regulates a number of proteins involved in the apoptotic process. To find new Akt interactors, we performed a two-hybrid screening in yeast using full-length Akt cDNA as bait and a human cDNA heart library as prey. Among 200 clones obtained, two of them were identified as coding for the c-FLIP<subscript>L</subscript> protein. c-FLIP<subscript>L</subscript> is an endogenous inhibitor of death receptor-induced apoptosis through the caspase-8 pathway. Using co-immunoprecipitation experiments of either transfected or endogenous proteins, we confirmed the interaction between Akt and c-FLIP<subscript>L</subscript>. Furthermore, we observed that c-FLIP<subscript>L</subscript> overexpression interferes with Gsk3-β phosphorylation levels. Moreover, through its effects on Gsk3β, c-FLIP<subscript>L</subscript> overexpression in cancer cells induced resistance to tumor necrosis factor-related apoptosis-inducing ligand (TRAIL). This effect was mediated by the regulation of p27<superscript>Kip1</superscript> and caspase-3 expression. These results indicate the existence of a new mechanism of resistance to TRAIL in cancer cells, and unexpected functions of c-FLIP<subscript>L</subscript>. [ABSTRACT FROM AUTHOR]
- Subjects :
- SERINE proteinases
PROTEIN kinases
APOPTOSIS
DNA
TUMOR necrosis factors
CANCER cells
Subjects
Details
- Language :
- English
- ISSN :
- 13509047
- Volume :
- 17
- Issue :
- 12
- Database :
- Complementary Index
- Journal :
- Cell Death & Differentiation
- Publication Type :
- Academic Journal
- Accession number :
- 55204536
- Full Text :
- https://doi.org/10.1038/cdd.2010.65