Polyamines regulate eukaryotic initiation factor 4E-binding protein 1 gene transcription.
Difluoromethylornithine-induced polyamine depletion produced a significant fall in the rate of 4E-BP1 gene transcription in IEC-6 cells, without a change in stability of the 4E-BP1 message. The effect was reversed by the addition of exogenous putrescine. Decreased 4E-BP1 gene transcription produced a concomitant fall in steady-state concentration of the 4E-BP1 protein. Segments of the 4E-BP1 gene 5' flanking sequence were inserted into a GFP reporter construct. While all the segments containing the first 500 nucleotides 5' to exon 1 were capable of driving GFP expression, two regions (between -2465 and -1965, and between -896 and 511) did so in a polyamine-dependent manner. Steady-state concentration of ornithine decarboxylase (ODC), the first enzyme in the polyamine biosynthetic pathway, was increased in response to polyamine depletion. These data provide a mechanism by which polyamines affect transcription of the 4E-BP1 gene, which in turn affect translation of ODC and perhaps other cap-dependent proteins.[1]References
- Polyamines regulate eukaryotic initiation factor 4E-binding protein 1 gene transcription. Stephenson, A.H., Christian, J.F., Seidel, E.R. Biochem. Biophys. Res. Commun. (2004) [Pubmed]
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