Growth-dependent repression of human adenine nucleotide translocator-2 (ANT2) transcription: evidence for the participation of Smad and Sp family proteins in the NF1-dependent repressor complex.
NF1 (nuclear factor 1) binds to two upstream elements of the human ANT2 (adenine nucleotide translocator-2) promoter and actively represses expression of the gene in growth-arrested diploid skin fibroblasts [Luciakova, Barath, Poliakova, Persson and Nelson (2003) J. Biol. Chem. 278, 30624-30633]. ChIP (chromatin immunoprecipitation) and co-immunoprecipitation analyses of nuclear extracts ... from growth-arrested and growth-activated diploid cells demonstrate that NF1, when acting as a repressor, is part of a multimeric complex that also includes Smad and Sp-family proteins. This complex appears to be anchored to both the upstream NF1-repressor elements and the proximal promoter, Sp1-dependent activation elements in growth-arrested cells. In growth-activated cells, the repressor complex dissociates and NF1 leaves the promoter. As revealed by co-immunoprecipitation experiments, NF1-Smad4-Sp3 complexes are present in nuclear extracts only from growth-inhibited cells, suggesting that the growth-state-dependent formation of these complexes is not an ANT2 promoter-specific event. Consistent with the role of Smad proteins in the repression complex, TGF-beta (transforming growth factor-beta) can fully repress ANT2 transcription in normally growing fibroblasts. Finally, pull-down experiments of in vitro transcribed/translated NF1 isoforms by GST (glutathione transferase)-Smad and GST-Smad MH fusion proteins indicate direct physical interactions between members of the two families. These findings suggest a possible functional relationship between the NF1 and Smad proteins that has not been previously observed.
Mesh Terms:
Adenine Nucleotide Translocator 2, Cell Proliferation, Cells, Cultured, Culture Media, Serum-Free, Down-Regulation, Humans, Models, Biological, Multigene Family, Multiprotein Complexes, Neurofibromin 1, Promoter Regions, Genetic, Protein Binding, Repressor Proteins, Smad Proteins, Sp Transcription Factors, Transcription, Genetic
Adenine Nucleotide Translocator 2, Cell Proliferation, Cells, Cultured, Culture Media, Serum-Free, Down-Regulation, Humans, Models, Biological, Multigene Family, Multiprotein Complexes, Neurofibromin 1, Promoter Regions, Genetic, Protein Binding, Repressor Proteins, Smad Proteins, Sp Transcription Factors, Transcription, Genetic
Biochem. J.
Date: May. 15, 2008
PubMed ID: 18215124
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