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.
Stephenson
A H
AH
Department of Physiology, Brody School of Medicine, East Carolina University, Greenville, NC 27858, USA.
Christian
J F
JF
Seidel
E R
ER
D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology; D001483:Base Sequence; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D018797:Cell Cycle Proteins; D002460:Cell Line; D002467:Cell Nucleus / Q000378:metabolism; D018076:DNA, Complementary / Q000378:metabolism; D000518:Eflornithine / Q000494:pharmacology; D039642:Eukaryotic Initiation Factors; D017930:Genes, Reporter; D047908:Intracellular Signaling Peptides and Proteins; D051379:Mice; D008969:Molecular Sequence Data; D041681:NIH 3T3 Cells; D009955:Ornithine Decarboxylase / Q000378:metabolism; D010750:Phosphoproteins / Q000235:genetics / Q000378:metabolism*; D011073:Polyamines / Q000737:chemistry*; D016133:Polymerase Chain Reaction; D011700:Putrescine / Q000494:pharmacology; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D020218:Response Elements; D012260:Ribonucleases / Q000378:metabolism; D013997:Time Factors; D014158:Transcription, Genetic
D048868:Adaptor Proteins, Signal Transducing; D000970:Antineoplastic Agents; D002352:Carrier Proteins; D018797:Cell Cycle Proteins; D018076:DNA, Complementary; C499527:Eif4ebp1 protein, mouse; C499526:Eif4ebp1 protein, rat; D039642:Eukaryotic Initiation Factors; D047908:Intracellular Signaling Peptides and Proteins; D010750:Phosphoproteins; D011073:Polyamines; D012333:RNA, Messenger; D012260:Ribonucleases; D009955:Ornithine Decarboxylase; D011700:Putrescine; D000518:Eflornithine