Regulation of CCAAT/enhancer-binding protein-β isoform synthesis by alternative translational initiation at multiple AUG start sites

W. Xiong, C. C. Hsieh, A. J. Kurtz, J. P. Rabek, John Papaconstantinou

Research output: Contribution to journalArticle

53 Citations (Scopus)

Abstract

The mRNA of the intronless, single-copy CCAAT/ enhancer-binding protein-β (C/EBPβ) gene encodes several isoforms that have truncated transcription activation domains. This occurs by the alternative translational initiation (ATI) at multiple AUG start sites. The C/EBPβ mRNA has four in-frame AUGs and an internal out-of-frame AUG associated with a small open reading frame (sORF). Initiation of translation at the in-frame AUGs forms 40-kDa (AUG-1), 35-kDa (AUG-2), 20-kDa (AUG-3) and 8.5-kDa (AUG-4) isoforms. We show that in COS-1 cells the 20-kDa isoform is not a product of proteolysis of the higher molecular weight isoforms. The sORF contains an AUG and termination signal that may produce the oligopeptide MPPAAARRL. Our studies suggest that ATI involves three mRNA structural features: (i) the cap structure, (ii) the context of the Kozak sequences that flank the AUG and (iii) the integrity of the sORF. We propose that formation of C/EBPβ isoforms is accomplished by a leaky ribosomal scanning mechanism that facilitates ATI of multiple internal AUGs.

Original languageEnglish (US)
Pages (from-to)3087-3098
Number of pages12
JournalNucleic Acids Research
Volume29
Issue number14
StatePublished - Jul 15 2001

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CCAAT-Enhancer-Binding Proteins
Protein Isoforms
Open Reading Frames
Messenger RNA
Oligopeptides
COS Cells
Transcriptional Activation
Proteolysis
Molecular Weight
Genes

ASJC Scopus subject areas

  • Genetics

Cite this

Regulation of CCAAT/enhancer-binding protein-β isoform synthesis by alternative translational initiation at multiple AUG start sites. / Xiong, W.; Hsieh, C. C.; Kurtz, A. J.; Rabek, J. P.; Papaconstantinou, John.

In: Nucleic Acids Research, Vol. 29, No. 14, 15.07.2001, p. 3087-3098.

Research output: Contribution to journalArticle

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