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The RNA-Binding Protein KSRP Promotes Decay of

The RNA-Binding Protein KSRP Promotes Decay of b -Catenin mRNA and Is Inactivated by PI3K-AKT Signaling. Roberto Gherzi et al. PLoS Biol . (2006). Decay of ARE-containing mRNA.

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The RNA-Binding Protein KSRP Promotes Decay of

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  1. The RNA-Binding Protein KSRP Promotes Decay of b-Catenin mRNA and Is Inactivated by PI3K-AKT Signaling Roberto Gherzi et al. PLoS Biol. (2006)

  2. Decay of ARE-containing mRNA AU-rich element (AREs), located in the 3’untranslated region (3’UTR) of many short-lived transcripts, promote mRNA degradation. The process of mRNA decay is integral to the posttranscriptional control of gene expression. Carol J. Wilusz and Jeffrey Wilusz. Trends Genet. (2004)

  3. What is KSRP? FBP2 was identified as an ARE-BP in Jurkat cell extracts that could be UV cross-linked to the IL-2 3’UTR. FBP2 is also known as KH-type splicing regulatory protein (KSRP). Dean JL. et al. Cell Signal. (2004 )

  4. Function of KSRP 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) KSRP targets c-fos, NOSII, TNF-a, IL-2 mRNA for rapid degradation by binding to an AU-rich element (ARE). 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)

  5. Scheme of PI3K-AKT signaling http://www.cellsignal.com/reference/pathway/pdfs/Akt_PKB.pdf

  6. Cross-talks between Wnt and PI3K-AKT pathway Activated Akt by Wnt bound to the Axin-GSK3b complex in the presence of Dvl, phosphorylated GSK3b and increased free b-catenin levels. Fukumoto S. et al. J Biol Chem. (2001) Insulin and IGF-1 to activate the b-catenin pathway through GSK-3b inhibition by PI3K-AKT pathway. Desbois-Mouthon C. et al. Oncogene. (2001) Akt phosphorylates b-catenin, which results in 14-3-3z binding and stabilization of b-catenin. Tian Q. et al. Proc Natl Acad Sci U S A. (2004) 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)

  7. mRNA Encoding b-Catenin Is Labile and Is Stabilized by LiCl and Wnt-3A

  8. PI3K-AKT Signaling Stabilizes b-Catenin mRNA and Increases Its Expression

  9. PI3K-AKT Signaling Stabilizes b-Catenin mRNA and Increases Its Expression

  10. Insulin Stabilizes b-Catenin mRNA and Increases Its Expression

  11. KSRP Is Phosphorylated by AKT in Serine 193

  12. KSRP Is Required for b-Catenin mRNA Degradation

  13. KSRP Phosphorylation by AKT Promotes Its Interaction with 14-3-3 and Affects Its mRNA-Destabilizing Function

  14. AKT Activation Affects KSRP-Exosome Interaction GST-KH1-4

  15. AKT P KSRP KSRP 14-3-3 14-3-3 14-3-3 14-3-3 P P P P KSRP KSRP KSRP KSRP PARN ARE AAAAAAAAAAAA Summary AKT phosphorylates KSRP, induces its interaction with 14-3-3, and prevents KSRP interaction with the exosome. Decay of b-catenin mRNA by KSRP is inactivated.

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