Endoplasmic reticulum stress-induced formation of transcription factor complex ERSF including NF-Y (CBF) and activating transcription factors 6alpha and 6beta that activates the mammalian unfolded protein response.
The levels of molecular chaperones and folding enzymes in the endoplasmic reticulum (ER) are controlled by a transcriptional induction process termed the unfolded protein response (UPR). The mammalian UPR is mediated by the cis-acting ER stress response element (ERSE), the consensus sequence of which is CCAAT-N(9)-CCACG. We recently proposed that ... ER stress response factor (ERSF) binding to ERSE is a heterologous protein complex consisting of the constitutive component NF-Y (CBF) binding to CCAAT and an inducible component binding to CCACG and identified the basic leucine zipper-type transcription factors ATF6alpha and ATF6beta as inducible components of ERSF. ATF6alpha and ATF6beta produced by ER stress-induced proteolysis bind to CCACG only when CCAAT is bound to NF-Y, a heterotrimer consisting of NF-YA, NF-YB, and NF-YC. Interestingly, the NF-Y and ATF6 binding sites must be separated by a spacer of 9 bp. We describe here the basis for this strict requirement by demonstrating that both ATF6alpha and ATF6beta physically interact with NF-Y trimer via direct binding to the NF-YC subunit. ATF6alpha and ATF6beta bind to the ERSE as a homo- or heterodimer. Furthermore, we showed that ERSF including NF-Y and ATF6alpha and/or beta and capable of binding to ERSE is indeed formed when the cellular UPR is activated. We concluded that ATF6 homo- or heterodimers recognize and bind directly to both the DNA and adjacent protein NF-Y and that this complex formation process is essential for transcriptional induction of ER chaperones.
Mesh Terms:
Activating Transcription Factor 6, Base Sequence, Basic-Leucine Zipper Transcription Factors, Binding Sites, CCAAT-Binding Factor, Consensus Sequence, DNA, DNA Primers, DNA-Binding Proteins, Dimerization, Endoplasmic Reticulum, G-Box Binding Factors, Hela Cells, Humans, Macromolecular Substances, Models, Biological, Molecular Chaperones, Mutation, Oxidative Stress, Protein Folding, Protein Structure, Quaternary, Protein Subunits, Transcription Factors
Activating Transcription Factor 6, Base Sequence, Basic-Leucine Zipper Transcription Factors, Binding Sites, CCAAT-Binding Factor, Consensus Sequence, DNA, DNA Primers, DNA-Binding Proteins, Dimerization, Endoplasmic Reticulum, G-Box Binding Factors, Hela Cells, Humans, Macromolecular Substances, Models, Biological, Molecular Chaperones, Mutation, Oxidative Stress, Protein Folding, Protein Structure, Quaternary, Protein Subunits, Transcription Factors
Mol. Cell. Biol.
Date: Feb. 01, 2001
PubMed ID: 11158310
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