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Repression of transcriptional activity of C/EBPα by E2F-DP complexes

Item Type:Article
Title:Repression of transcriptional activity of C/EBPα by E2F-DP complexes
Creators Name:Zaragoza, K. and Bégay, V. and Schuetz, A. and Heinemann, U. and Leutz, A.
Abstract:The transcription factor CCAAT/enhancer-binding protein alpha (C/EBPalpha) coordinates proliferation arrest and differentiation of myeloid progenitors, adipocytes, hepatocytes, keratinocytes, cells of the lung, and placenta. C/EBPalpha transactivates lineage specific differentiation genes and inhibits proliferation by repressing E2F-regulated genes. The myeloproliferative C/EBPalpha BRM2 mutant serves as a paradigm for recurrent human C-terminal bZIP C/EBPalpha mutations that are involved in acute myeloid leukemogenesis. BRM2 fails to repress E2F and to induce adipogenesis and granulopoiesis. Data presented here show that, independently of pocket proteins, C/EBPalpha interacts with the dimerization partner (DP) of E2F and that C/EBPalpha-E2F/DP interaction prevents both, binding of C/EBPalpha to its cognate sites on DNA and transactivation of C/EBP target genes. The BRM2 mutant, in addition, exhibits enhanced interaction with E2F-DP and reduced affinity towards DNA yet retains transactivation potential and differentiation competence that becomes exposed when E2F/DP levels are low. Our data suggest a tripartite balance between C/EBPalpha, E2F/DP and pocket proteins in the control of proliferation, differentiation and tumorigenesis.
Keywords:Amino Acid Sequence, Binding Sites, CCAAT-Enhancer-Binding Protein-alpha, Cell Differentiation, Cell Line, Consensus Sequence, DNA, E2F Transcription Factors, Gene Knockdown Techniques, Biological Models, Molecular Sequence Data, Mutant Proteins, Mutation, Genetic Promoter Regions, Protein Binding, Protein Multimerization, Repressor Proteins, Retinoblastoma Protein, Genetic Transcription, Animals, Mice
Source:Molecular and Cellular Biology
ISSN:0270-7306
Publisher:American Society for Microbiology (U.S.A.)
Volume:30
Number:9
Page Range:2293-2304
Date:May 2010
Official Publication:https://doi.org/10.1128/MCB.01619-09
PubMed:View item in PubMed

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