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Translational control of PPARβ in macrophage differentiation
Author(s) -
Cambiaghi Tavane David,
Luchessi Augusto Ducati,
Curi Rui
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.1_supplement.998.6
Subject(s) - eif4e , internal ribosome entry site , dephosphorylation , translational regulation , translation (biology) , phosphorylation , messenger rna , protein biosynthesis , untranslated region , ribosomal binding site , eukaryotic translation , microbiology and biotechnology , chemistry , biology , biochemistry , gene , phosphatase
Previous studies have shown that the 5′‐UTR of the PPARβ transcript negatively regulates its expression. The mechanisms of translational control of PPARβ expression mediated by its 5′‐UTR in PMA‐differentiated THP‐1 cells were investigated. PMA treatment of THP‐1 cells caused a time‐dependent increase PPARβ production. A polysomal profile assay revealed reduction of the protein synthesis in response to PMA, indicating inhibition of translation initiation. The activity of eIF2α was analyzed by western blotting and showed an intensive dephosphorylation followed by a recover of the phosphorylation state during the period of higher production of PPARβ. This recover was preceded by dephosphorylation of eIF4E‐binding protein (4E‐BP). This process inhibits cap‐dependent translation initiation since dephosphorylated 4E‐BP binds to eIF4E. The mRNAs that contain internal ribosome entry site (IRES) are preferentially translated under conditions where eIF4E activity is decreased. A structural analysis of the PPARβ 5′‐UTR showed the presence of seven uORFs (upstream open reading frames) that can control translation of this transcript. Therefore PPARβ expression may be controlled by both mechanisms. Financial support: FAPESP, CNPq and CAPES.