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| Identification of the cis-acting endoplasmic reticulum stress response element responsible for transcriptional induction of mammalian glucose-regulated proteins - Involvement of basic leucine zipper transcription factors |
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| Author(s): Yoshida H, Haze K, Yanagi H, Yura T, Mori K |
| Source: JOURNAL OF BIOLOGICAL CHEMISTRY Volume: 273 Issue: 50 Pages: 33741-33749 Published: DEC 11 1998 |
| Times Cited: 426 References: 55 |
| Abstract: When unfolded proteins accumulate in the endoplasmic reticulum (ER), transcription of glucose-regulated proteins (GRPs) representing ER-resident molecular chaperones is markedly induced via the unfolded protein response (UPR) pathway. In contrast to recent progress in the analysis of yeast UPR, both cis-acting elements and transactivators responsible for mammalian UPR have remained obscure, Here, we analyzed the promoter regions of human GRP78, GRP94, and calreticulin genes and identified a novel element designated the ER stress response element (ERSE), ERSE, with a consensus of CCAATN(9)CCACG, was shown to be necessary and sufficient for induction of these GRPs, Using yeast one-hybrid screening, we isolated a human cDNA encoding a basic leucine zipper (bZIP) protein, ATF6, as a putative ERSE-binding protein. When overexpressed in HeLa cells, ATF6 enhanced transcription of GRP genes in an ERSE-dependent manner, whereas CREB-RP, another bZIP protein closely related ito ATF6, specifically inhibited GRP induction. Endogenous ATF6 constitutively expressed as a 90-kDa protein was converted to a 50-kDa protein in ER-stressed cells, which appeared to be important for the cellular response to ER stress. These results suggest that, as in yeast, bZIP proteins are involved in mammalian UPR, acting through newly defined ERSE. |
| Document Type: Article |
| Language: English |
| Reprint Address: Mori, K (reprint author), HSP Res Inst, Kyoto Res Pk, Kyoto 6008813, Japan |
Addresses:
1. HSP Res Inst, Kyoto 6008813, Japan |
| Publisher: AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC, 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA |
| Subject Category: Biochemistry & Molecular Biology |
| IDS Number: 146YY |
| ISSN: 0021-9258 |
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