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PPARδ is a regulator of autophagy by its phosphorylation

Oncogene volume 39, pages 4844–4853 (2020)Cite this article

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Abstract

In response to nutrient deficiency, autophagy degrades cytoplasmic materials and organelles in lysosomes, which is nutrient recycling, whereas activation of EGFR mediates autophagy suppression in response to growth factors. It is unclear whether PPARδ could be the regulator of autophagy in response to active EGFR. Here we found that EGFR induced PPARδ phosphorylation at tyrosine-108 leading to increased binding of LC3 to PPARδ by its LIR (LC3 interacting region) motif, consequently, inhibited autophagic flux. Conversely, EGFR inhibitor treatment reversed this event. Furthermore, EGFR-mediated PPARδ phosphorylation at tyrosine-108 led to autophagy inhibition and tumor growth. These findings suggest that PPARδ serves as a regulator of autophagy by its phosphorylation.

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Fig. 1: EGFR induces PPARδ phosphorylation.
Fig. 2: PPARδ-Y108 phosphorylation inhibits autophagy.
Fig. 3: PPARδ-Y108 phosphorylation enhances the binding of PPARδ to LC3.
Fig. 4: The LIR motif of PPARδ is required for LC3 binding.
Fig. 5: PPARδ-Y108 phosphorylation promotes tumor growth.
Fig. 6: The model of PPARδ phosphorylation regulates autophagy.

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Acknowledgements

This work was supported by the National Natural Science Foundation of China (81672711, 81972618); Postgraduate Research & Practice Innovation Program of Jiangsu Province (KYCX18_2218).

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  1. These authors contributed equally: Qian Gou, Yidan Jiang, Runyun Zhang

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  1. Institute of Life Science, Jiangsu University, Zhenjiang, Jiangsu Province, 212013, People’s Republic of China

    Qian Gou, Yidan Jiang, Runyun Zhang, Ying Xu, Huihui Xu, Wenbo Zhang, Juanjuan Shi & Yongzhong Hou

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Gou, Q., Jiang, Y., Zhang, R. et al. PPARδ is a regulator of autophagy by its phosphorylation. Oncogene 39, 4844–4853 (2020). https://doi.org/10.1038/s41388-020-1329-x

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