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Titolo:
Activation of ATF6 and an ATF6 DNA binding site by the endoplasmic reticulum stress response
Autore:
Wang, Y; Shen, JS; Arenzana, N; Tirasophon, W; Kaufman, RJ; Prywes, R;
Indirizzi:
Columbia Univ, Dept Biol Sci, New York, NY 10027 USA Columbia Univ New York NY USA 10027 Dept Biol Sci, New York, NY 10027 USA Univ Michigan, Med Ctr, Dept Biol Chem, Ann Arbor, MI 48109 USA Univ Michigan Ann Arbor MI USA 48109 t Biol Chem, Ann Arbor, MI 48109 USA Univ Michigan, Med Ctr, Howard Hughes Med Inst, Ann Arbor, MI 48109 USA Univ Michigan Ann Arbor MI USA 48109 es Med Inst, Ann Arbor, MI 48109 USA
Titolo Testata:
JOURNAL OF BIOLOGICAL CHEMISTRY
fascicolo: 35, volume: 275, anno: 2000,
pagine: 27013 - 27020
SICI:
0021-9258(20000901)275:35<27013:AOAAAA>2.0.ZU;2-0
Fonte:
ISI
Lingua:
ENG
Soggetto:
UNFOLDED-PROTEIN RESPONSE; FAMILIAL ALZHEIMERS-DISEASE; CCAAT REGULATORY ELEMENT; EPIDERMAL GROWTH-FACTOR; TRANSCRIPTION FACTOR; TRANSMEMBRANE PROTEIN; INTRACELLULAR DOMAIN; MISSENSE MUTATIONS; GRP78/BIP PROMOTER; NUCLEAR ACCESS;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
44
Recensione:
Indirizzi per estratti:
Indirizzo: Prywes, R Columbia Univ, Dept Biol Sci, Fairchild 813B,MC 2420,1212 Amsterdam Ave, New York, NY 10027 USA Columbia Univ Fairchild 813B,MC 2420,1212 Amsterdam Ave New York NY USA 10027
Citazione:
Y. Wang et al., "Activation of ATF6 and an ATF6 DNA binding site by the endoplasmic reticulum stress response", J BIOL CHEM, 275(35), 2000, pp. 27013-27020

Abstract

ATF6 is a member of the basic-leucine zipper family of transcription factors. It contains a transmembrane domain and is located in membranes of the endoplasmic reticulum, ATF6 has been implicated in the endoplasmic reticulum(ER) stress response pathway since it can activate expression of GRP78 andother genes induced by the ER stress response. ER stress appears to activate ATF6 by cleavage from the ER membrane and translocation to the nucleus, However, direct DNA binding by ATF6 had not been demonstrated. In this report, we have identified a consensus DNA binding sequence for ATF6. This siteis related to but distinct from ATF1/CREB binding sites. The site was placed in a reporter gene and was specifically activated by ATF6 overexpressionand was strongly induced by the ER stress response. A dominant negative form of ATF6 blocked ER stress induction of both ATF6 site and GRP78 reportergenes. We further found that GAL4-ATF6 could be activated by ER stress. These results demonstrate that ATF6 is a direct target of the ER stress response. A proximal sensor of the ER stress response, human IRE1 (hIRE1), was sufficient to activate the ATF6 reporter gene, while a dominant negative form of hIRE1 blocked ER stress activation, suggesting that: hIRE1 is upstreamof ATF6 in the ER stress signaling pathway.

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Documento generato il 24/09/20 alle ore 10:31:49