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J Biol Chem, Vol. 273, Issue 16, 9552-9560, April 17, 1998
From the Advanced BioScience Laboratories-Basic Research Program,
NCI-Frederick Cancer Research and Development Center, National
Institutes of Health, Frederick, Maryland 21702-1201
CCAAT/enhancer-binding protein (C/EBP)
Inhibition of CCAAT/Enhancer-binding Protein
and 
Translation by Upstream Open Reading Frames
is a
bZIP transcription factor whose expression is restricted to specific
cell types. Analysis of C/EBP mRNA and protein levels in various
mammalian cells indicates that expression of this gene is controlled
both transcriptionally and post-transcriptionally. We report here that C/EBP translation is repressed in several cell lines by an
evolutionarily conserved upstream open reading frame (uORF), which acts
in cis to inhibit C/EBP translation. Mutations that
disrupt the uORF completely abolished translational repression of
C/EBP. The related c/ebp
gene also contains an uORF
that suppresses translation. The length of the spacer sequence between
the uORF terminator and the ORF initiator codon (7 bases in all
c/ebp genes and 4 bases in c/ebp
homologs) is precisely conserved. The effects of insertions, deletions,
and base substitutions in the C/EBP spacer showed that both the
length and nucleotide sequence of the spacer are important for
efficient translational repression. Our data indicate that the uORFs
regulate translation of full-length C/EBP and C/EBP and do not
play a role in generating truncated forms of these proteins, as has
been suggested by start site multiplicity models.
Copyright © 1998 by The American Society for Biochemistry and Molecular Biology, Inc.
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