| | |  | | | | Record from Web of Science® | | | | | | |
| Proapoptotic BAX and BAK modulate the unfolded protein response by a direct interaction with IRE1 alpha |
|
|
| Author(s): Hetz C, Bernasconi P, Fisher J, Lee AH, Bassik MC, Antonsson B, Brandt GS, Iwakoshi NN, Schinzel A, Glimcher LH, Korsmeyer SJ |
| Source: SCIENCE Volume: 312 Issue: 5773 Pages: 572-576 Published: APR 28 2006 |
| Times Cited: 115 References: 32 |
| Abstract: Accumulation of misfolded protein in the endoplasmic reticulum (ER) triggers an adaptive stress response-termed the unfolded protein response (UPR)-mediated by the ER transmembrane protein kinase and endoribonuclease inositol-requiring enzyme-1 alpha (IRE1 alpha). We investigated UPR signaling events in mice in the absence of the proapoptotic BCL-2 family members BAX and BAK [double knockout (DKO)]. DKO mice responded abnormally to tunicamycin-induced ER stress in the liver, with extensive tissue damage and decreased expression of the IRE1 substrate X-box-binding protein 1 and its target genes. ER-stressed DKO cells showed deficient IRE1a signaling. BAX and BAK formed a protein complex with the cytosolic domain of IRE1 alpha that was essential for IRE1 alpha activation. Thus, BAX and BAK function at the ER membrane to activate IRE1 alpha signaling and to provide a physical link between members of the core apoptotic pathway and the UPR. |
| Document Type: Article |
| Language: English |
| Reprint Address: Hetz, C (reprint author), Dana Farber Canc Inst, Howard Hughes Med Inst, Boston, MA 02115 USA |
Addresses:
1. Dana Farber Canc Inst, Howard Hughes Med Inst, Boston, MA 02115 USA
2. Harvard Univ, Sch Med, Boston, MA 02115 USA
3. Harvard Univ, Sch Publ Hlth, Dept Immunol & Infect Dis, Boston, MA 02115 USA
4. Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA
5. Serono Pharmaceut Res Inst, CH-1228 Plan Les Ouates, Switzerland
6. Brandeis Univ, Rosenstiel Ctr, Dept Biochem, Waltham, MA 02454 USA
7. Brandeis Univ, Rosenstiel Ctr, Dept Chem, Waltham, MA 02454 USA |
| Publisher: AMER ASSOC ADVANCEMENT SCIENCE, 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA |
| Subject Category: Multidisciplinary Sciences |
| IDS Number: 039HN |
| ISSN: 0036-8075 |
| DOI: 10.1126/science.1123480 |
|
| | | | | | | | | Record from Web of Science® | | | | | | | | | |