Molecular mechanisms underlying the BIRC6-mediated regulation of apoptosis and autophagy.

Autor: Liu SS; State Key Laboratory of Cognitive Neuroscience & Learning and Ministry of Education Key Laboratory of Cell Proliferation & Regulation Biology, College of Life Sciences, Beijing Normal University, 19 Xinjiekouwai Avenue, Beijing, 100875, China., Jiang TX; State Key Laboratory of Cognitive Neuroscience & Learning and Ministry of Education Key Laboratory of Cell Proliferation & Regulation Biology, College of Life Sciences, Beijing Normal University, 19 Xinjiekouwai Avenue, Beijing, 100875, China., Bu F; State Key Laboratory of Cognitive Neuroscience & Learning and Ministry of Education Key Laboratory of Cell Proliferation & Regulation Biology, College of Life Sciences, Beijing Normal University, 19 Xinjiekouwai Avenue, Beijing, 100875, China., Zhao JL; State Key Laboratory of Cognitive Neuroscience & Learning and Ministry of Education Key Laboratory of Cell Proliferation & Regulation Biology, College of Life Sciences, Beijing Normal University, 19 Xinjiekouwai Avenue, Beijing, 100875, China., Wang GF; State Key Laboratory of Cognitive Neuroscience & Learning and Ministry of Education Key Laboratory of Cell Proliferation & Regulation Biology, College of Life Sciences, Beijing Normal University, 19 Xinjiekouwai Avenue, Beijing, 100875, China., Yang GH; State Key Laboratory of Cognitive Neuroscience & Learning and Ministry of Education Key Laboratory of Cell Proliferation & Regulation Biology, College of Life Sciences, Beijing Normal University, 19 Xinjiekouwai Avenue, Beijing, 100875, China., Kong JY; State Key Laboratory of Cognitive Neuroscience & Learning and Ministry of Education Key Laboratory of Cell Proliferation & Regulation Biology, College of Life Sciences, Beijing Normal University, 19 Xinjiekouwai Avenue, Beijing, 100875, China., Qie YF; State Key Laboratory of Cognitive Neuroscience & Learning and Ministry of Education Key Laboratory of Cell Proliferation & Regulation Biology, College of Life Sciences, Beijing Normal University, 19 Xinjiekouwai Avenue, Beijing, 100875, China., Wen P; State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing, Jiangsu, 211198, China.; College of Life Sciences, Anhui Medical University, Hefei, Anhui, 230032, China., Fan LB; College of Life Sciences, Anhui Medical University, Hefei, Anhui, 230032, China., Li NN; State Key Laboratory of Membrane Biology, Peking-Tsinghua Joint Center for Life Sciences, School of Life Sciences, Peking University, Beijing, 100871, China. ningningli@pku.edu.cn., Gao N; State Key Laboratory of Membrane Biology, Peking-Tsinghua Joint Center for Life Sciences, School of Life Sciences, Peking University, Beijing, 100871, China. gaon@pku.edu.cn., Qiu XB; State Key Laboratory of Cognitive Neuroscience & Learning and Ministry of Education Key Laboratory of Cell Proliferation & Regulation Biology, College of Life Sciences, Beijing Normal University, 19 Xinjiekouwai Avenue, Beijing, 100875, China. xqiu@bnu.edu.cn.; State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing, Jiangsu, 211198, China. xqiu@bnu.edu.cn.
Jazyk: angličtina
Zdroj: Nature communications [Nat Commun] 2024 Jan 30; Vol. 15 (1), pp. 891. Date of Electronic Publication: 2024 Jan 30.
DOI: 10.1038/s41467-024-45222-1
Abstrakt: Procaspase 9 is the initiator caspase for apoptosis, but how its levels and activities are maintained remains unclear. The gigantic Inhibitor-of-Apoptosis Protein BIRC6/BRUCE/Apollon inhibits both apoptosis and autophagy by promoting ubiquitylation of proapoptotic factors and the key autophagic protein LC3, respectively. Here we show that BIRC6 forms an anti-parallel U-shaped dimer with multiple previously unannotated domains, including a ubiquitin-like domain, and the proapoptotic factor Smac/DIABLO binds BIRC6 in the central cavity. Notably, Smac outcompetes the effector caspase 3 and the pro-apoptotic protease HtrA2, but not procaspase 9, for binding BIRC6 in cells. BIRC6 also binds LC3 through its LC3-interacting region, probably following dimer disruption of this BIRC6 region. Mutation at LC3 ubiquitylation site promotes autophagy and autophagic degradation of BIRC6. Moreover, induction of autophagy promotes autophagic degradation of BIRC6 and caspase 9, but not of other effector caspases. These results are important to understand how the balance between apoptosis and autophagy is regulated under pathophysiological conditions.
(© 2024. The Author(s).)
Databáze: MEDLINE
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