PPARbeta and the Translational Status of PMA‐differentiated THP‐1 Cells

The differentiation of THP‐1 cells in macrophages, induced by PMA, is associated to overexpression of peroxisome proliferator‐activated receptor b (PPARb). Previous studies have shown that the PPARb 5′ UTR negatively regulates its expression. In our study the translational status of PMA‐differentiated THP‐1 cells was investigated in association to overexpression of PPARb. Putative compatible Kosak initiation codons were identified in the PPARb uORFs and could be involved in the inhibitory effect of 5′ UTR. Decreased incorporation of L‐[U‐14C]Leucine in proteins revealed that the overproduction of PPARb in PMA‐differentiated THP‐1 cells coincides with a global decrease in the protein synthesis process. Translation impairment was confirmed by polysome profile assay. An intense dephosphorylation of 4E‐BP by PMA treatment was observed. Dephosphorylated 4E‐BP causes inhibition of eIF4E cap‐dependent translation initiation and favors IRES‐dependent translation. The PPARb 5′ UTR structure has some characteristics that resemble the one described for IRES. Therefore, the PPARb production may be controlled by IRES and the high production of PPARb occurs concomitantly with cap‐dependent translation inhibition.