CCAAT/enhancer binding protein alpha (CIEBP alpha) is an important mediator of mouse C/EBP beta protein isoform production

Both CCAAT/enhancer binding protein cr (C/EBP alpha) and C/EBP beta are int ronless, yet can create various N-terminally truncated protein products wit h distinct DNA binding and transactivation potentials. These proteins can b e generated via two distinct mechanisms, one translational and the other po st-translational. In the translational mechanism, there is alternative tran slational start site selection of the different AUG codons present in the s ingle messenger RNA (mRNA) species via a process of leaky ribosome scanning . Additionally, a post-translational method of isoform formation, through s pecific proteolytic cleavage of the full length protein has also been descr ibed. In this manuscript, we present evidence that the production of C/EBP beta protein isoforms in the neonatal mouse liver is regulated by C/EBP alp ha. In C/EBP alpha knockout mice, the predominant C/EBP beta proteins are t he larger 38- and 35-kd isoforms, whereas wild-type animals primarily posse ss the smaller 21- and 14-kd isoforms. These C/EBP alpha-dependent differen ces are liver specific, not present in lung or adipose tissues, and present at day 18 of development. Additionally, we show that induction of C/EBP al pha expression leads to an increase in the production of the 21-kd C/EBP be ta isoform in cell culture studies, As the various C/EBP beta protein isofo rms have different transcriptional capabilities, it is important to underst and the regulation of the production of these isoforms. Our observations su ggest a novel role for the C/EBP alpha transcription factor in this process .