CCAAT/enhancer-binding protein mRNA is translated into multiple proteins with different transcription activation potentials.
The CCAAT/enhancer-binding protein (C/EBP) alpha is a leucine zipper protein that is preferentially expressed in certain cell types, such as adipocytes and hepatocytes. Here we show that C/EBP alpha mRNA is translated into two major proteins, C/EBP-42 and C/EBP-30, that differ in their content of N-terminal amino acid sequences. These results are best explained by a ribosome-scanning mechanism in which a fraction of ribosomes ignore the first two AUGs and initiate translation at an AUG located 351 nt downstream of the first one. Because C/EBP-30, the translation product initiated at the third AUG, is devoid of the potent transcription-activation domain contained in C/EBP-42, the former protein stimulates transcription from the mouse albumin promoter much less efficiently than the latter. The gene encoding the liver-enriched transcriptional-activator protein LAP (C/EBP-beta) has also been shown to issue two proteins, LAP and the liver-enriched transcriptional-inhibitory protein LIP, with different transcription-activation potentials. The production of multiple proteins from a single mRNA is not only shared between different C/EBP family members but also appears to be conserved in vertebrate evolution.
Ossipow
V
V
Department of Molecular Biology, University of Geneva, Switzerland.
Descombes
P
P
Schibler
U
U
D000345:Affinity Labels; D000595:Amino Acid Sequence; D000818:Animals; D001386:Azides; D001483:Base Sequence; D022762:CCAAT-Enhancer-Binding Proteins; D017124:Conserved Sequence; D004268:DNA-Binding Proteins / Q000096:biosynthesis* / Q000302:isolation & purification / Q000378:metabolism; D005822:Genetic Vectors; D006801:Humans; D008099:Liver / Q000378:metabolism*; D008969:Molecular Sequence Data; D009687:Nuclear Proteins / Q000096:biosynthesis* / Q000302:isolation & purification / Q000378:metabolism; D015345:Oligonucleotide Probes / Q000138:chemical synthesis; D014176:Protein Biosynthesis; D012333:RNA, Messenger / Q000378:metabolism*; D051381:Rats; D011994:Recombinant Proteins / Q000096:biosynthesis / Q000378:metabolism; D013045:Species Specificity; D014157:Transcription Factors / Q000096:biosynthesis*; D014544:Uridine Triphosphate / Q000031:analogs & derivatives; D014714:Vertebrates / Q000378:metabolism
D000345:Affinity Labels; D001386:Azides; D022762:CCAAT-Enhancer-Binding Proteins; D004268:DNA-Binding Proteins; D009687:Nuclear Proteins; D015345:Oligonucleotide Probes; D012333:RNA, Messenger; D011994:Recombinant Proteins; D014157:Transcription Factors; C072279:5-azidouridine-5'-triphosphate; D014544:Uridine Triphosphate