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

被引:253
作者
Yoshida, H
Okada, T
Haze, K
Yanagi, H
Yura, T
Negishi, M
Mori, K
机构
[1] Kyoto Univ, Grad Sch Biostudies, Sakyo Ku, Kyoto 6068304, Japan
[2] HSP Res Inst, Shimogyo Ku, Kyoto 6008813, Japan
关键词
D O I
10.1128/MCB.21.4.1239-1248.2001
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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 ATF6 alpha and ATF6 beta as inducible components of ERSF. ATF6 alpha and ATF6 beta 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 ATF6 alpha and ATF6 beta physically interact with NF-Y trimer via direct binding to the NF-YC subunit. ATF6 alpha and ATF6 beta bind to the ERSE as a homo- or heterodimer. Furthermore, we showed that ERSF including NF-Y and ATF6 alpha. 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.
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收藏
页码:1239 / 1248
页数:10
相关论文
共 28 条
[11]   ATF6 as a transcription activator of the endoplasmic reticulum stress element: Thapsigargin stress-induced changes and synergistic interactions with NF-Y and YY1 [J].
Li, MQ ;
Baumeister, P ;
Roy, B ;
Phan, T ;
Foti, D ;
Luo, SZ ;
Lee, AS .
MOLECULAR AND CELLULAR BIOLOGY, 2000, 20 (14) :5096-5106
[12]   STRESS INDUCTION OF THE MAMMALIAN GRP78/BIP PROTEIN GENE - IN-VIVO GENOMIC FOOTPRINTING AND IDENTIFICATION OF P70CORE FROM HUMAN NUCLEAR EXTRACT AS A DNA-BINDING COMPONENT SPECIFIC TO THE STRESS REGULATORY ELEMENT [J].
LI, WW ;
SISTONEN, L ;
MORIMOTO, RI ;
LEE, AS .
MOLECULAR AND CELLULAR BIOLOGY, 1994, 14 (08) :5533-5546
[13]  
LI WWF, 1993, J BIOL CHEM, V268, P12003
[14]   CCAAT-binding factor NF-Y and RFX are required for in vivo assembly of a nucleoprotein complex that spans 250 base pairs: the invariant chain promoter as a model [J].
Linhoff, MW ;
Wright, KL ;
Ting, JPY .
MOLECULAR AND CELLULAR BIOLOGY, 1997, 17 (08) :4589-4596
[15]  
LITTLEWOOD T, 1995, PROTEIN PROFILE TRAN, V2
[16]   Role of the CCAAT-binding protein CBF/NF-Y in transcription [J].
Maity, SN ;
de Crombrugghe, B .
TRENDS IN BIOCHEMICAL SCIENCES, 1998, 23 (05) :174-178
[17]   A NOVEL CREB FAMILY GENE TELOMERIC OF HLA-DRA IN THE HLA COMPLEX [J].
MIN, J ;
SHUKLA, H ;
KOZONO, H ;
BRONSON, SK ;
WEISSMAN, SM ;
CHAPLIN, DD .
GENOMICS, 1995, 30 (02) :149-156
[18]   Tripartite management of unfolded proteins in the endoplasmic reticulum [J].
Mori, K .
CELL, 2000, 101 (05) :451-454
[19]   FUNCTION OF MAJOR HISTOCOMPATIBILITY COMPLEX CLASS-II PROMOTERS REQUIRES COOPERATIVE BINDING BETWEEN FACTORS RFX AND NF-Y [J].
REITH, W ;
SIEGRIST, CA ;
DURAND, B ;
BARRAS, E ;
MACH, B .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1994, 91 (02) :554-558
[20]   The mammalian endoplasmic reticulum stress response element consists of an evolutionarily conserved tripartite structure and interacts with a novel stress-inducible complex [J].
Roy, B ;
Lee, AS .
NUCLEIC ACIDS RESEARCH, 1999, 27 (06) :1437-1443