Metabolic-stress-induced rearrangement of the 14-3-3ζ interactome promotes autophagy via a ULK1- and AMPK-regulated 14-3-3ζ interaction with phosphorylated Atg9
| Autor: | John T. Prince, David J. Panek, Gideon N. Logan, Vajira K. Weerasekara, Andrew D. Mathis, David G. Broadbent, J. Will Thompson, David M. Thomson, Jeffrey B. Mortenson, Joshua L. Andersen |
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| Rok vydání: | 2014 |
| Předmět: |
Autophagosome
Vesicular Transport Proteins Autophagy-Related Proteins Biology AMP-Activated Protein Kinases Protein Serine-Threonine Kinases Interactome AMP-activated protein kinase Stress Physiological Cell Line Tumor Phagosomes Autophagy Serine Autophagy-Related Protein-1 Homolog Humans Phosphorylation Molecular Biology Intracellular Signaling Peptides and Proteins AMPK Membrane Proteins Cell Biology Articles ULK1 Cell Hypoxia Cell biology HEK293 Cells 14-3-3 Proteins biology.protein HeLa Cells |
| Zdroj: | Molecular and cellular biology. 34(24) |
| ISSN: | 1098-5549 |
| Popis: | 14-3-3ζ promotes cell survival via dynamic interactions with a vast network of binding partners, many of which are involved in stress regulation. We show here that hypoxia (low glucose and oxygen) triggers a rearrangement of the 14-3-3ζ interactome to favor an interaction with the core autophagy regulator Atg9A. Our data suggest that the localization of mammalian Atg9A to autophagosomes requires phosphorylation on the C terminus of Atg9A at S761, which creates a 14-3-3ζ docking site. Under basal conditions, this phosphorylation is maintained at a low level and is dependent on both ULK1 and AMPK. However, upon induction of hypoxic stress, activated AMPK bypasses the requirement for ULK1 and mediates S761 phosphorylation directly, resulting in an increase in 14-3-3ζ interactions, recruitment of Atg9A to LC3-positive autophagosomes, and enhanced autophagosome production. These data suggest a novel mechanism whereby the level of autophagy induction can be modulated by AMPK/ULK1-mediated phosphorylation of mammalian Atg9A. |
| Databáze: | OpenAIRE |
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