Polyamines regulate eukaryotic initiation factor 4E-binding protein 1 gene transcription

• Published in: Biochemical and biophysical research communications 2004-10, Vol.323 (1), p.204-212
• Main Authors: Stephenson, A.H., Christian, J.F., Seidel, E.R.
• Format: Article
• Language: English
• Subjects: Animals; Antineoplastic Agents - pharmacology; Base Sequence; Carrier Proteins - genetics; Carrier Proteins - metabolism; Cell Line; Cell Nucleus - metabolism; DNA, Complementary - metabolism; Eflornithine - pharmacology; Genes, Reporter; Mice; Molecular Sequence Data; NIH 3T3 Cells; Ornithine Decarboxylase - metabolism; Phosphoproteins - genetics; Phosphoproteins - metabolism; Polyamines - chemistry; Polymerase Chain Reaction; Putrescine - pharmacology; Rats; Response Elements; Ribonucleases - metabolism; RNA, Messenger - metabolism; Time Factors; Transcription, Genetic
• ISSN: 0006-291X; 1090-2104
• DOI: 10.1016/j.bbrc.2004.08.076

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.