期刊
EMBO JOURNAL
卷 30, 期 21, 页码 4465-4478出版社
WILEY
DOI: 10.1038/emboj.2011.318
关键词
autophagy; bax inhibitor-1(B1-1); inositol requiring kinase 1 alpha (IRE1 alpha); jun-terminal kinase (JNK); microtubule-associated protein 1 light chain 3 (LC3)
资金
- FONDECYT [1100176, 3100112, 1100366, 1090272, 1070377]
- FONDAP [15010006]
- Millennium Institute [P09-015-F]
- Alzheimer's Association
- Michael J Fox Foundation
- ICGEB
- CONICYT
- Millennium Nucleus [P07-011-F]
Both autophagy and apoptosis are tightly regulated processes playing a central role in tissue homeostasis. Bax inhibitor 1 (BI-1) is a highly conserved protein with a dual role in apoptosis and endoplasmic reticulum (ER) stress signalling through the regulation of the ER stress sensor inositol requiring kinase 1 alpha (IRE1 alpha). Here, we describe a novel function of BI-1 in the modulation of autophagy. BI-1-deficient cells presented a faster and stronger induction of autophagy, increasing LC3 flux and autophagosome formation. These effects were associated with enhanced cell survival under nutrient deprivation. Repression of autophagy by BI-1 was dependent on cJun-N terminal kinase (JNK) and IRE1 alpha expression, possibly due to a displacement of TNF-receptor associated factor-2 (TRAF2) from IRE1 alpha. Targeting BI-1 expression in flies altered autophagy fluxes and salivary gland degradation. BI-1 deficiency increased flies survival under fasting conditions. Increased expression of autophagy indicators was observed in the liver and kidney of bi-1-deficient mice. In summary, we identify a novel function of BI-1 in multicellular organisms, and suggest a critical role of BI-1 as a stress integrator that modulates autophagy levels and other interconnected homeostatic processes. The EMBO Journal (2011) 30, 4465-4478. doi:10.1038/emboj.2011.318; Published online 16 September 2011
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