Endoplasmic reticulum stress-induced formation of transcription factor complex ERSF including NF-Y (CBF) and activating transcription factors 6α and 6β that activates …

H Yoshida, T Okada, K Haze, H Yanagi… - … and cellular biology, 2001 - Taylor & Francis
H Yoshida, T Okada, K Haze, H Yanagi, T Yura, M Negishi, K Mori
Molecular and cellular biology, 2001Taylor & Francis
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-N9-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 …
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-N9-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 ATF6α and ATF6β as inducible components of ERSF. ATF6α and ATF6β 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 ATF6α and ATF6β physically interact with NF-Y trimer via direct binding to the NF-YC subunit. ATF6α and ATF6β bind to the ERSE as a homo- or heterodimer. Furthermore, we showed that ERSF including NF-Y and ATF6α and/or β 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.
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