| First Author | Kannan-Thulasiraman P | Year | 2008 |
| Journal | Biochem Biophys Res Commun | Volume | 368 |
| Issue | 4 | Pages | 983-9 |
| PubMed ID | 18280804 | Mgi Jnum | J:134219 |
| Mgi Id | MGI:3785143 | Doi | 10.1016/j.bbrc.2008.02.028 |
| Citation | Kannan-Thulasiraman P, et al. (2008) Role of the translational repressor 4E-BP1 in the regulation of p21(Waf1/Cip1) expression by retinoids. Biochem Biophys Res Commun 368(4):983-9 |
| abstractText | The mechanisms by which retinoids regulate initiation of mRNA translation for proteins that mediate their biological effects are not known. We have previously shown that all-trans-retinoic acid (ATRA) induces mTOR-mediated activation of the p70 S6 kinase, suggesting the existence of a mechanism by which retinoids may regulate mRNA translation. We now demonstrate that treatment of acute promyelocytic leukemia (APL)-derived NB4 cells with ATRA results in dissociation of the translational repressor 4E-BP1 from the eukaryotic initiation factor eIF4E, and subsequent formation of eIF4G-eIF4E complexes. We also show that siRNA-mediated inhibition of 4E-BP1 expression enhances ATRA-dependent upregulation of p21(Waf1/Cip1), a protein that plays a key role in the induction of retinoid-dependent responses. Our data also establish that ATRA- or cis-RA-dependent p21(Waf1/Cip1) protein expression is enhanced in mouse embryonic fibroblasts with targeted disruption of the 4e-bp1 gene, in the absence of any effects on the transcriptional regulation of the p21(Waf1/Cip1) gene. Moreover, generation of ATRA- or cis-retinoic acid (cis-RA)-antiproliferative responses is enhanced in 4E-BP1 knockout cells. Altogether, these findings strongly suggest a key regulatory role for the translational repressor 4E-BP1 in the generation of retinoid-dependent functional responses. |
