Genome-wide screen identifies signaling pathways that regulate autophagy during
Caenorhabditis elegans development |
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Authors: | Bin Guo Xinxin Huang Peipei Zhang Linxiang Qi Qianqian Liang Xuebo Zhang Jie Huang Bin Fang Wenru Hou Jinghua Han Hong Zhang |
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Institution: | 1College of Life Sciences, China Agricultural
University, Beijing, China;2State Key Laboratory of Biomacromolecules, Institute of
Biophysics, Chinese Academy of Sciences, Beijing, China;3National Institute of Biological Sciences, Beijing, China |
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Abstract: | The mechanisms that coordinate the regulation of autophagy with developmental signaling during
multicellular organism development remain largely unknown. Here, we show that impaired function of
ribosomal protein RPL-43 causes an accumulation of SQST-1 aggregates in the larval intestine, which
are removed upon autophagy induction. Using this model to screen for autophagy regulators, we
identify 139 genes that promote autophagy activity upon inactivation. Various signaling pathways,
including Sma/Mab TGF-β signaling, lin-35/Rb signaling, the XBP-1-mediated
ER stress response, and the ATFS-1-mediated mitochondrial stress response, regulate the expression
of autophagy genes independently of the TFEB homolog HLH-30. Our study thus provides a framework for
understanding the role of signaling pathways in regulating autophagy under physiological
conditions.Subject Categories: Autophagy & Cell Death; Signal Transduction; Membrane & Intracellular Transport |
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Keywords: | autophagy Caenorhabditis elegans ER stress mitochondrial stress Rb |
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