Pdpk1-KO Mouse

Pdpk1, also known as 3-phosphoinositide dependent protein kinase 1, is a phosphorylation-regulated kinase. It plays a central role in activating multiple signaling pathways, such as the AKT1-MTOR pathway, and is involved in various cellular processes like autophagy, cell proliferation, and metabolism [1,2,4,5].

In autophagy, Pdpk1 can act as a SUMOylation-regulated kinase to turn on macroautophagy. SUMOylated Pdpk1 regulates its phosphorylation and AKT1-MTOR pathway activation, while non-SUMOylated Pdpk1 tethers LC3 to the endoplasmic reticulum to initiate autophagy [1]. In hepatocellular carcinoma, AQP3 accumulation induced by FBXW5 knockdown leads to Pdpk1 degradation, inactivating the AKT-MTOR pathway and inducing autophagic death [2]. Also, Pdpk1 phosphorylation of SQSTM1 at T138 by coronavirus M protein promotes mitophagy over virophagy, and a Pdpk1-targeting peptide can inhibit RNA virus replication [3].

In conclusion, Pdpk1 is crucial in regulating autophagy-related processes and has implications in virus-host interactions and cancer-related autophagic cell death. Understanding Pdpk1's function through in vivo models like those in the studies provides insights into potential therapeutic targets for treating virus-induced diseases and certain cancers.