Characterization of CCAAT/enhancer-binding protein α as a cyclic AMP- responsive nuclear regulator

William J. Roesler, Edwards Park, Pamela J. McFie

Research output: Contribution to journalArticle

54 Citations (Scopus)

Abstract

The α isoform of CCAAT/enhancer-binding protein (C/EBPα) is a transcription factor that regulates expression of genes linked to adipose differentiation and hepatic nutrient metabolism. Recently, our laboratory has characterized a role for C/EBPα in mediating hormonal responsiveness. For example, the cAMP responsiveness of the phosphoenolpyruvate carboxykinase gene promoter in liver requires synergism among the cAMP response element- binding protein (CREB), C/EBPα, and activator protein-1. In the present study, we show that C/EBPα can functionally substitute for CREB in this cAMP response unit, i.e. cAMP responsiveness can occur in the absence of CREB. This observation is physiologically relevant since both CREB and C/EBPα have been shown to bind with high affinity to the cAMP response element in this particular promoter. Structure/function analysis of C/EBPα identified specific mutations that differentially affected its constitutive and protein kinase A-inducible activities. This finding suggests that the mechanism whereby C/EBPα mediates constitutive transactivation is distinct from that whereby it mediates cAMP responsiveness. These data support the hypothesis that C/EBPα plays a critical role in metabolism, in part by participating in the hormonal regulation of expression of metabolically important genes.

Original languageEnglish (US)
Pages (from-to)14950-14957
Number of pages8
JournalJournal of Biological Chemistry
Volume273
Issue number24
DOIs
StatePublished - Jun 12 1998

Fingerprint

CCAAT-Enhancer-Binding Proteins
Cyclic AMP
Cyclic AMP Response Element-Binding Protein
Genes
Metabolism
Phosphoenolpyruvate
Liver
Transcription Factor AP-1
Response Elements
Cyclic AMP-Dependent Protein Kinases
Transcriptional Activation
Nutrients
Protein Isoforms
Transcription Factors
Gene Expression
Food
Mutation

All Science Journal Classification (ASJC) codes

  • Biochemistry

Cite this

Characterization of CCAAT/enhancer-binding protein α as a cyclic AMP- responsive nuclear regulator. / Roesler, William J.; Park, Edwards; McFie, Pamela J.

In: Journal of Biological Chemistry, Vol. 273, No. 24, 12.06.1998, p. 14950-14957.

Research output: Contribution to journalArticle

@article{25bb186a96224c6cba2ca129cc181701,
title = "Characterization of CCAAT/enhancer-binding protein α as a cyclic AMP- responsive nuclear regulator",
abstract = "The α isoform of CCAAT/enhancer-binding protein (C/EBPα) is a transcription factor that regulates expression of genes linked to adipose differentiation and hepatic nutrient metabolism. Recently, our laboratory has characterized a role for C/EBPα in mediating hormonal responsiveness. For example, the cAMP responsiveness of the phosphoenolpyruvate carboxykinase gene promoter in liver requires synergism among the cAMP response element- binding protein (CREB), C/EBPα, and activator protein-1. In the present study, we show that C/EBPα can functionally substitute for CREB in this cAMP response unit, i.e. cAMP responsiveness can occur in the absence of CREB. This observation is physiologically relevant since both CREB and C/EBPα have been shown to bind with high affinity to the cAMP response element in this particular promoter. Structure/function analysis of C/EBPα identified specific mutations that differentially affected its constitutive and protein kinase A-inducible activities. This finding suggests that the mechanism whereby C/EBPα mediates constitutive transactivation is distinct from that whereby it mediates cAMP responsiveness. These data support the hypothesis that C/EBPα plays a critical role in metabolism, in part by participating in the hormonal regulation of expression of metabolically important genes.",
author = "Roesler, {William J.} and Edwards Park and McFie, {Pamela J.}",
year = "1998",
month = "6",
day = "12",
doi = "10.1074/jbc.273.24.14950",
language = "English (US)",
volume = "273",
pages = "14950--14957",
journal = "Journal of Biological Chemistry",
issn = "0021-9258",
publisher = "American Society for Biochemistry and Molecular Biology Inc.",
number = "24",

}

TY - JOUR

T1 - Characterization of CCAAT/enhancer-binding protein α as a cyclic AMP- responsive nuclear regulator

AU - Roesler, William J.

AU - Park, Edwards

AU - McFie, Pamela J.

PY - 1998/6/12

Y1 - 1998/6/12

N2 - The α isoform of CCAAT/enhancer-binding protein (C/EBPα) is a transcription factor that regulates expression of genes linked to adipose differentiation and hepatic nutrient metabolism. Recently, our laboratory has characterized a role for C/EBPα in mediating hormonal responsiveness. For example, the cAMP responsiveness of the phosphoenolpyruvate carboxykinase gene promoter in liver requires synergism among the cAMP response element- binding protein (CREB), C/EBPα, and activator protein-1. In the present study, we show that C/EBPα can functionally substitute for CREB in this cAMP response unit, i.e. cAMP responsiveness can occur in the absence of CREB. This observation is physiologically relevant since both CREB and C/EBPα have been shown to bind with high affinity to the cAMP response element in this particular promoter. Structure/function analysis of C/EBPα identified specific mutations that differentially affected its constitutive and protein kinase A-inducible activities. This finding suggests that the mechanism whereby C/EBPα mediates constitutive transactivation is distinct from that whereby it mediates cAMP responsiveness. These data support the hypothesis that C/EBPα plays a critical role in metabolism, in part by participating in the hormonal regulation of expression of metabolically important genes.

AB - The α isoform of CCAAT/enhancer-binding protein (C/EBPα) is a transcription factor that regulates expression of genes linked to adipose differentiation and hepatic nutrient metabolism. Recently, our laboratory has characterized a role for C/EBPα in mediating hormonal responsiveness. For example, the cAMP responsiveness of the phosphoenolpyruvate carboxykinase gene promoter in liver requires synergism among the cAMP response element- binding protein (CREB), C/EBPα, and activator protein-1. In the present study, we show that C/EBPα can functionally substitute for CREB in this cAMP response unit, i.e. cAMP responsiveness can occur in the absence of CREB. This observation is physiologically relevant since both CREB and C/EBPα have been shown to bind with high affinity to the cAMP response element in this particular promoter. Structure/function analysis of C/EBPα identified specific mutations that differentially affected its constitutive and protein kinase A-inducible activities. This finding suggests that the mechanism whereby C/EBPα mediates constitutive transactivation is distinct from that whereby it mediates cAMP responsiveness. These data support the hypothesis that C/EBPα plays a critical role in metabolism, in part by participating in the hormonal regulation of expression of metabolically important genes.

UR - http://www.scopus.com/inward/record.url?scp=0032510987&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0032510987&partnerID=8YFLogxK

U2 - 10.1074/jbc.273.24.14950

DO - 10.1074/jbc.273.24.14950

M3 - Article

VL - 273

SP - 14950

EP - 14957

JO - Journal of Biological Chemistry

JF - Journal of Biological Chemistry

SN - 0021-9258

IS - 24

ER -