Document Detail


Evidence for posttranscriptional regulation of C/EBPalpha and C/EBPbeta isoform expression during the lipopolysaccharide-mediated acute-phase response.
MedLine Citation:
PMID:  8628296     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The mRNAs of the CCAAT/enhancer-binding trans-activator proteins (C/EBPalpha and C/EBPbeta) serve as templates for the differential translation of several isoforms which have specific transcriptional regulatory functions. By using an oligonucleotide corresponding to the C/EBP binding site of the mouse alpha1-acid glycoprotein promoter, we detected multiple forms of C/EBPalpha and C/EBP++ beta proteins in the mouse liver that have DNA-binding activity. By using specific antisera, we detected C/EBPalphas with molecular masses of 42, 38, 30, and 20 kDa that have DNA-binding activity. The pool levels of the 42- and 30-kDa isoforms were high in control nuclear extracts and decreased significantly after lipopolysaccharide (LPS) treatment. The binding activity and protein levels of the 20-kDa isoform are low in controls and increase dramatically after LPS treatment. C/EBPbeta isoforms with molecular masses of 35, 20, and 16 kDa were also detected. The 35-kDa pool level did not change whereas the 20-kDa isoform was strongly induced in response to LPS. Western (immunoblot) and Southwestern (DNA-protein) analyses show that p42 C/EBPalpha forms specific complexes with the alpha1-acid glycoprotein oligonucleotide in control nuclear extract and that p20 C/EBP beta forms complexes in LPS-treated liver. Our studies suggest that synthesis of specific C/EBPalpha and C/EBPbeta isoforms occurred in the normal liver in vivo and that LPS mediated a differential initiation and inhibition of translation at specific AUG sites within each mRNA. The qualitative and quantitative changes in C/EBPalpha and C/EBPbeta isoform pool levels suggest that LPS or an LPS-stimulated factor can regulate the selection of AUG start sites for both activation and repression of translation. This regulation appears to involve an LPS-mediated down-regulation of initiation at the first AUG codon of the 42-kDa C/EBPalpha and dramatic translational up-regulation at the fifth AUG codon of the 20-kDa C/EBPalpha and the third AUG codon of the 20-kDa C/EBPbeta. These regulatory events suggest the existence of proteins that may act as translational trans-acting factors.
Authors:
M R An; C C Hsieh; P D Reisner; J P Rabek; S G Scott; D T Kuninger; J Papaconstantinou
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Publication Detail:
Type:  Journal Article; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Molecular and cellular biology     Volume:  16     ISSN:  0270-7306     ISO Abbreviation:  Mol. Cell. Biol.     Publication Date:  1996 May 
Date Detail:
Created Date:  1996-06-21     Completed Date:  1996-06-21     Revised Date:  2009-11-18    
Medline Journal Info:
Nlm Unique ID:  8109087     Medline TA:  Mol Cell Biol     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  2295-306     Citation Subset:  IM    
Affiliation:
Department of Human Biological Chemistry and Genetics, University of Texas Medical Branch, Galveston, 77555, USA.
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MeSH Terms
Descriptor/Qualifier:
Amino Acid Sequence
Animals
Base Sequence
CCAAT-Enhancer-Binding Proteins
Cell Nucleus / metabolism
DNA-Binding Proteins / biosynthesis*
Electrophoresis, Polyacrylamide Gel
Gene Expression / drug effects*
Immune Sera
Immunoblotting
Kinetics
Lipopolysaccharides / pharmacology*
Liver / metabolism*
Male
Mice
Mice, Inbred BALB C
Molecular Sequence Data
Nuclear Proteins / biosynthesis*,  isolation & purification,  metabolism
Oligodeoxyribonucleotides
Orosomucoid / biosynthesis,  genetics
Peptide Fragments / chemical synthesis,  immunology
Promoter Regions, Genetic
Protein Biosynthesis / drug effects*
RNA, Messenger / metabolism
Transcription Factors / biosynthesis*
Transcription, Genetic
Grant Support
ID/Acronym/Agency:
P01 AG10514/AG/NIA NIH HHS
Chemical
Reg. No./Substance:
0/CCAAT-Enhancer-Binding Proteins; 0/DNA-Binding Proteins; 0/Immune Sera; 0/Lipopolysaccharides; 0/Nuclear Proteins; 0/Oligodeoxyribonucleotides; 0/Orosomucoid; 0/Peptide Fragments; 0/RNA, Messenger; 0/Transcription Factors
Comments/Corrections

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