title: Unraveling the roles of Atg4 proteases from autophagy modulation to targeted cancer therapy.
abstract: Atg4 proteases are cysteine proteases, which are well known for their crucial roles in the lipidation and delipidation of LC3 during the autophagy process. At least four human Atg4 homologs have been reported according to their sequence homology to the yeast Saccharomyces cerevisiae (Sc) Atg4. Accumulating evidence has recently indicated that abnormal expression levels of some human Atg4 proteins occur in several types of cancer cells, which may be closely related to tumor progression, tumor suppression and cancer therapy resistance. In this review, we focus on highlighting the pivotal roles of the human Atg4 proteases in the LC3 conjugation system and their major function in autophagy. Moreover, we further explore the roles of human Atg4 proteases as potential novel targets for cancer therapy. Taken together, these findings would shed light on elucidating the key roles of Atg4 proteases from autophagy modulation to targeted cancer therapy.
authors.affiliation: State Key Laboratory of Biotherapy and Cancer Center/Collaborative Innovation Center of Biotherapy, West China Hospital, Sichuan University, Chengdu 610041, China.
authors.forename: Lan
authors.initials: L
authors.lastname: Zhang
authors.affiliation: State Key Laboratory of Biotherapy and Cancer Center/Collaborative Innovation Center of Biotherapy, West China Hospital, Sichuan University, Chengdu 610041, China.
authors.forename: Jingjing
authors.initials: J
authors.lastname: Li
authors.affiliation: State Key Laboratory of Biotherapy and Cancer Center/Collaborative Innovation Center of Biotherapy, West China Hospital, Sichuan University, Chengdu 610041, China.
authors.forename: Liang
authors.initials: L
authors.lastname: Ouyang
authors.affiliation: State Key Laboratory of Biotherapy and Cancer Center/Collaborative Innovation Center of Biotherapy, West China Hospital, Sichuan University, Chengdu 610041, China. Electronic address: liubo2400@scu.edu.cn.
authors.forename: Bo
authors.initials: B
authors.lastname: Liu
authors.affiliation: Department of Pharmacology, School of Pharmaceutical Sciences, Central South University, Changsha 410008, China. Electronic address: chengyan0677@163.com.
authors.forename: Yan
authors.initials: Y
authors.lastname: Cheng
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use; D001343:Autophagy / Q000187:drug effects; D000071183:Autophagy-Related Proteins; D003546:Cysteine Endopeptidases / Q000235:genetics / Q000378:metabolism*; D015853:Cysteine Proteinase Inhibitors / Q000627:therapeutic use; D015195:Drug Design; D006801:Humans; D058990:Molecular Targeted Therapy; D009369:Neoplasms / Q000188:drug therapy / Q000201:enzymology* / Q000235:genetics / Q000473:pathology; D011487:Protein Conformation; D011499:Protein Processing, Post-Translational; D015398:Signal Transduction; D013329:Structure-Activity Relationship
chemical_list: D000970:Antineoplastic Agents; D000071183:Autophagy-Related Proteins; D015853:Cysteine Proteinase Inhibitors; C474025:ATG4A protein, human; C507524:ATG4B protein, human; C543490:ATG4D protein, human; D003546:Cysteine Endopeptidases
keywords: Apoptosis; Atg4 protease; Atg8/LC3; Autophagy; Targeted cancer therapy