CCAAT ENHANCER-BINDING PROTEIN MESSENGER-RNA IS TRANSLATED INTO MULTIPLE PROTEINS WITH DIFFERENT TRANSCRIPTION ACTIVATION POTENTIALS

The CCAAT/enhancer-binding protein (C/EBP) alpha is a leucine zipper p rotein that is preferentially expressed in certain cell types, such as adipocytes and hepatocytes. Here we show that C/EBP alpha mRNA is tra nslated 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 b est explained by a ribosome-scanning mechanism in whkh a fraction of r ibosomes ignore the first two AUGs and initiate translation at an AUG located 351 nt downstream of the first one. Because C/EBP-30, the tran slation product initiated at the third AUG, is devoid of the potent tr anscription-activation domain contained in C/EBP-42, the former protei n stimulates transcription from the mouse albumin promoter much less e fficiendy than the latter. The gene encoding the liver-enriched transc riptional-activator protein LAP (C/EBP-beta) has also been shown to is sue two proteins, LAP and the liver-enriched transcriptional-inhibitor y 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 conserv ed in vertebrate evolution.