UNC51-like kinase 1, autophagic regulator and cancer therapeutic target

Abstract

Autophagy, the cell process of self-digestion, plays a pivotal role in maintaining energy homoeostasis and protein synthesis. When required, it causes degradation of long-lived proteins and damaged organelles, indicating that it may play a dual role in cancer, by both protecting against and promoting cell death. The autophagy-related gene (Atg) family, with more than 35 members, regulates multiple stages of the process. Serine/threonine protein kinase Atg1 in yeast, for example, can interact with other ATG gene products, functioning in autophagosome formation. One mammalian homologue of Atg1, UNC-51-like kinase 1 (ULK1) and its related complex ULK1-mAtg13-FIP200 can mediate autophagy under nutrient-deprived conditions, by protein-protein interactions and post-translational modifications. Although specific mechanisms of how ULK1 and its complex transduces upstream signals to the downstream central autophagy pathways is not fully understood, past studies have indicated that ULK1 can both suppress and promote tumour growth under different conditions. Here, we summarize some properties of ULK1 which can regulate autophagy in cancer, which may shed new light on future cancer therapy strategies, utilizing ULK1 as a potential new target.