ER Stress Induces Cleavage of Membrane-Bound ATF6 by the Same Proteases that Process SREBPs
| Autor: | Utpal P. Davé, Ryutaro Komuro, Michael S. Brown, Xi Chen, Ron Prywes, Joseph L. Goldstein, Jin Ye, Robert B. Rawson |
|---|---|
| Rok vydání: | 2000 |
| Předmět: |
Proteases
Transcription Genetic medicine.medical_treatment Amino Acid Motifs Immunoblotting Molecular Sequence Data Biology Endoplasmic Reticulum Cell Line chemistry.chemical_compound Endopeptidases medicine Animals Humans Amino Acid Sequence RNA Messenger Endoplasmic Reticulum Chaperone BiP Molecular Biology Heat-Shock Proteins Protease ATF6 Tunicamycin Endoplasmic reticulum Serine Endopeptidases fungi Intracellular Signaling Peptides and Proteins Membrane Proteins Intracellular Membranes Cell Biology Activating Transcription Factor 6 Sterol regulatory element-binding protein Cell biology DNA-Binding Proteins chemistry Membrane protein Mutation CCAAT-Enhancer-Binding Proteins Unfolded protein response Thapsigargin lipids (amino acids peptides and proteins) Proprotein Convertases Carrier Proteins Sterol Regulatory Element Binding Protein 1 Protein Processing Post-Translational Sequence Alignment Molecular Chaperones Protein Binding Transcription Factors |
| Zdroj: | Molecular Cell. 6(6):1355-1364 |
| ISSN: | 1097-2765 |
| DOI: | 10.1016/s1097-2765(00)00133-7 |
| Popis: | ATF6 is a membrane-bound transcription factor that activates genes in the endoplasmic reticulum (ER) stress response. When unfolded proteins accumulate in the ER, ATF6 is cleaved to release its cytoplasmic domain, which enters the nucleus. Here, we show that ATF6 is processed by Site-1 protease (S1P) and Site-2 protease (S2P), the enzymes that process SREBPs in response to cholesterol deprivation. ATF6 processing was blocked completely in cells lacking S2P and partially in cells lacking S1P. ATF6 processing required the RxxL and asparagine/proline motifs, known requirements for S1P and S2P processing, respectively. Cells lacking S2P failed to induce GRP78, an ATF6 target, in response to ER stress. ATF6 processing did not require SCAP, which is essential for SREBP processing. We conclude that S1P and S2P are required for the ER stress response as well as for lipid synthesis. |
| Databáze: | OpenAIRE |
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