Institute of Life Science, Jiangsu University, Zhenjiang, Jiangsu Province, 212013, People's Republic of China.
Oncogene. 2020 Jun;39(25):4844-4853. doi: 10.1038/s41388-020-1329-x. Epub 2020 May 21.
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.
针对营养缺乏，自噬在溶酶体中降解细胞质物质和细胞器，这是营养回收，而 EGFR 的激活介导自噬抑制对生长因子的反应。目前尚不清楚 PPARδ 是否可以作为响应活性 EGFR 的自噬调节剂。在这里，我们发现 EGFR 诱导 PPARδ 酪氨酸-108 磷酸化，导致 LC3 通过其 LIR（LC3 相互作用区域）基序与 PPARδ 结合增加，从而抑制自噬通量。相反，EGFR 抑制剂处理逆转了这一事件。此外，EGFR 介导的 PPARδ 酪氨酸-108 磷酸化导致自噬抑制和肿瘤生长。这些发现表明，PPARδ 通过其磷酸化作为自噬的调节剂。
