自噬
ATG5型
生物
泛素连接酶
泛素
细胞生物学
平方毫米
平衡
细胞凋亡
基因
遗传学
作者
Hongchang Li,Chaonan Li,Weihua Zhai,Xin Zhang,Lei Li,Bo Wu,Biyue Yu,Pengfei Zhang,Jie Li,Chun-Ping Chu,Lingqiang Zhang
出处
期刊:Cell Reports
[Elsevier]
日期:2022-10-01
卷期号:41 (1): 111435-111435
被引量:2
标识
DOI:10.1016/j.celrep.2022.111435
摘要
Autophagy is essential for the maintenance of energy homeostasis and for survival during the neonatal starvation period. At birth, the trans-placental nutrient supply is suddenly interrupted, and neonates adapt to this adverse circumstance by activating autophagy. However, the mechanisms underlying the precise regulation of neonatal autophagy remain undefined. Here, we show that the destabilization of TP53 by the deubiquitylase ubiquitin-specific peptidase 10 (USP10) is essential for neonatal autophagy and survival. Usp10 deficiency results in decreased E3 ligase activity of MDM2 and accumulation of cytoplasmic TP53, which interferes with the conjugation of ATG12 and ATG5, the key autophagy-related genes, and ultimately inhibits autophagy in neonatal mice. Combined deletion of Tp53 and Usp10 recovers the nutrition supply and rescues the death phenotype of Usp10-deficient neonates. These findings reveal a role of the USP10-MDM2-TP53 axis in nutrient homeostasis and neonatal viability and provide insights into the long-perplexing mechanism by which cytoplasmic TP53 inhibits autophagy.
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