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The RNA-Binding Protein KSRP Promotes Decay of
-Catenin mRNA and Is Inactivated by PI3K-AKT Signaling
Roberto Gherzi et al. PLoS Biol. (2006)
Carol J. Wilusz and Jeffrey Wilusz. Trends Genet. (2004)
Decay of ARE-containing mRNA
The process of mRNA decay is integral to the posttranscriptionalcontrol of gene expression.
AU-rich element (AREs), located in the 3’untranslated region (3’UTR) of many short-lived transcripts, promote mRNA degradation.
FBP2 is also known as KH-type splicing regulatory protein (KSRP).
FBP2 was identified as an ARE-BP in Jurkat cell extracts that could be
UV cross-linked to the IL-2 3’UTR.
What is KSRP?
Dean JL. et al. Cell Signal. (2004 )
Barreau C. et al. Nucleic Acids Res. (2006)
p38-dependent phosphorylation of the mRNA decay-promoting factor KSRP controls the stability of select myogenic transcripts
Briata P. et al. Mol Cell. (2005)
KSRP targets c-fos, NOSII, TNF-, IL-2 mRNA for rapid degradation by binding to anAU-rich element (ARE).
KSRP, a KH domain-containing ARE-BP, is an essential factor for ARE-directed mRNA decay.
Gherzi R. et al. Mol Cell. (2004)
Hall MP. et al. Mol Biol Cell. (2004)
Function of KSRP
Cross-talks between Wnt and PI3K-AKT pathway
Akt phosphorylates -catenin, which results in 14-3-3 binding and stabilization of -catenin.
Tian Q. et al. Proc Natl Acad Sci U S A. (2004)
Activated Akt by Wnt bound to the Axin-GSK3 complex in the presence of Dvl, phosphorylated GSK3 and increased free -catenin levels.
Fukumoto S. et al. J Biol Chem. (2001)
Insulin and IGF-1 to activate the -catenin pathway through GSK-3 inhibition by PI3K-AKT pathway.
Desbois-Mouthon C. et al. Oncogene. (2001)
Wnt proteins prolong the survival of osteoblasts and uncommitted osteoblast progenitors via activation of the Src/ERK and PI3K/Akt signaling cascades.
Almeida M. et al. J Biol Chem. (2005)
The phosphatidyl inositol 3 kinases (PI3K)-Akt pathway is also involved in the Wnt3a-induced proliferation.
Kim SE. et al. Cell Signal. (2006)
KSRP Phosphorylation by AKT Promotes Its Interaction with 14-3-3 and Affects Its mRNA-Destabilizing Function