The C/EBP? LIP isoform rescues loss of C/EBP? function in the mouse.

ABSTRACT: The transcription factor C/EBP? regulates hematopoiesis, bone, liver, fat, and skin homeostasis, and female reproduction. C/EBP? protein expression from its single transcript occurs by alternative in-frame translation initiation at consecutive start sites to generate three isoforms, two long (LAP*, LAP) and one truncated (LIP), with the same C-terminal bZip dimerization domain. The long C/EBP? isoforms are considered gene activators, whereas the LIP isoform reportedly acts as a dominant-negative repressor. Here, we tested the putative repressor functions of the C/EBP? LIP isoform in mice by comparing monoallelic WT or LIP knockin mice with Cebpb knockout mice, in combination with monoallelic Cebpa mice. The C/EBP? LIP isoform was sufficient to function in coordination with C/EBP? in murine development, adipose tissue and sebocyte differentiation, and female fertility. Thus, the C/EBP? LIP isoform likely has more physiological functions than its currently known role as a dominant-negative inhibitor, which are more complex than anticipated.

SUBMITTER: Begay V 

PROVIDER: S-EPMC5976626 | biostudies-literature | 2018 May

REPOSITORIES: biostudies-literature