Author: ["Ying Zhao","Jing Yang","Wenjuan Liao","Xiangyu Liu","Hui Zhang","Shan Wang","Donglai Wang","Jingnan Feng","Li Yu","Wei-Guo Zhu"]
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Abstract
Autophagy is involved in tumour suppression. Cytoplasmic FoxO1 is acetylated in response to stress and binds the autophagy regulator Atg7 to promote autophagy, cell death and tumour suppression, independently of its transcriptional activity. Autophagy is characterized by the sequestration of bulk cytoplasm, including damaged proteins and organelles, and delivery of the cargo to lysosomes for degradation. Although the autophagic pathway is also linked to tumour suppression activity, the mechanism is not yet clear. Here we report that cytosolic FoxO1, a forkhead O family protein, is a mediator of autophagy. Endogenous FoxO1 was required for autophagy in human cancer cell lines in response to oxidative stress or serum starvation, but this process was independent of the transcriptional activity of FoxO1. In response to stress, FoxO1 was acetylated by dissociation from sirtuin-2 (SIRT2), a NAD+-dependent histone deacetylase, and the acetylated FoxO1 bound to Atg7, an E1-like protein, to influence the autophagic process leading to cell death. This FoxO1-modulated cell death is associated with tumour suppressor activity in human colon tumours and a xenograft mouse model. Our finding links the anti-neoplastic activity of FoxO1 and the process of autophagy.Cite this article
Zhao, Y., Yang, J., Liao, W. et al. Cytosolic FoxO1 is essential for the induction of autophagy and tumour suppressor activity. Nat Cell Biol 12, 665–675 (2010). https://doi.org/10.1038/ncb2069 