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Distinct role of Kruppel-like factor 11 in the regulation of prostaglandin E2 biosynthesis. J Biol Chem 2010 Apr 09;285(15):11433-44

Date

02/16/2010

Pubmed ID

20154088

Pubmed Central ID

PMC2857022

DOI

10.1074/jbc.M109.077065

Scopus ID

2-s2.0-77951214442 (requires institutional sign-in at Scopus site)   38 Citations

Abstract

Kruppel-like factor (KLF) proteins are emerging as key regulators of lipid metabolism, diabetes, and the biosynthesis of immunological cytokines. However, their role in the synthesis of prostaglandins, widely known biochemical mediators that act in a myriad of cell biological processes remain poorly understood. Consequently, in this study a comprehensive investigation at the cellular, biochemical, and molecular levels reveal that KLF11 inhibits prostaglandin E(2) synthesis via transcriptional silencing of the promoter of its biosynthetic enzyme, cytosolic phospholipase A2alpha. Mechanistically, KLF11 accomplishes this function by binding to the promoter via specific GC-rich sites and recruiting the Sin3-histone deacetylase chromatin remodeling complex. Further functional characterization reveals that this function of KLF11 can be reversed by epidermal growth factor receptor-AKT-mediated post-translational modification of threonine 56, a residue within its Sin3-binding domain. This is the first evidence supporting a relevant role for any KLF protein in doing both: transcriptionally inhibiting prostaglandin biosynthesis and its reversibility by an epidermal growth factor receptor-AKT signaling-mediated posttranslational mechanisms.

Author List

Buttar NS, DeMars CJ, Lomberk G, Ilyas SI, Bonilla-Velez J, Achra S, Rashtak S, Wang KK, Fernandez-Zapico ME, Urrutia R

Authors

Gwen Lomberk PhD Professor in the Surgery department at Medical College of Wisconsin
Raul A. Urrutia MD Center Director, Professor in the Surgery department at Medical College of Wisconsin




MESH terms used to index this publication - Major topics in bold

Animals
Apoptosis Regulatory Proteins
CHO Cells
Cell Cycle Proteins
Cell Line
Cell Proliferation
Chromatin
Cricetinae
Cricetulus
Dinoprostone
Epigenesis, Genetic
Humans
Lipids
Models, Biological
Models, Genetic
Phospholipases A2
Promoter Regions, Genetic
Protein Processing, Post-Translational
Repressor Proteins
Zinc Fingers