title: Tumor suppressor gene PDCD4 negatively regulates autophagy by inhibiting the expression of autophagy-related gene ATG5.
abstract: PDCD4 (programmed cell death protein 4), a suppressor of gene transcription and translation, plays a crucial inhibitory role in several types of human tumors. However, its underlying mechanisms remain unclear. Autophagy, an evolutionarily conserved catabolic process, maintains cellular homeostasis under stress conditions such as starvation and plays a crucial role in tumor initiation and progression. We report here that PDCD4 inhibits autophagy in multiple cell types both in vitro and in vivo, which in turn contributes to its tumor suppressor activity. Importantly, PDCD4 inhibits the expression of an essential autophagy related gene, ATG5 and the formation of an ATG12-ATG5 complex, and its ma3 domains are required for PDCD4-mediated inhibition of autophagy. Unlike most tumor suppressors that act as positive or dual regulators of autophagy, our findings indicate that PDCD4 negatively regulates autophagy by targeting ATG5, which provides a novel mechanism of tumor suppression.
authors.affiliation: Department of Immunology, Shandong University, School of Medicine, Shangdong, China.
authors.forename: Xingguo
authors.initials: X
authors.lastname: Song
authors.forename: Xia
authors.initials: X
authors.lastname: Zhang
authors.forename: Xiaoyan
authors.initials: X
authors.lastname: Wang
authors.forename: Faliang
authors.initials: F
authors.lastname: Zhu
authors.forename: Chun
authors.initials: C
authors.lastname: Guo
authors.forename: Qun
authors.initials: Q
authors.lastname: Wang
authors.forename: Yongyu
authors.initials: Y
authors.lastname: Shi
authors.forename: Jianing
authors.initials: J
authors.lastname: Wang
authors.forename: Youhai
authors.initials: Y
authors.lastname: Chen
authors.forename: Lining
authors.initials: L
authors.lastname: Zhang
mesh_terms: D000818:Animals; D051017:Apoptosis Regulatory Proteins / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D001343:Autophagy / Q000235:genetics*; D000071187:Autophagy-Related Protein 5; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D005786:Gene Expression Regulation; D006801:Humans; D051379:Mice; D008869:Microtubule-Associated Proteins / Q000235:genetics* / Q000378:metabolism; D008954:Models, Biological; D014176:Protein Biosynthesis / Q000235:genetics; D017434:Protein Structure, Tertiary; D016601:RNA-Binding Proteins / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D023041:Xenograft Model Antitumor Assays
chemical_list: C502778:ATG5 protein, human; D051017:Apoptosis Regulatory Proteins; D000071187:Autophagy-Related Protein 5; D008869:Microtubule-Associated Proteins; C114487:PDCD4 protein, human; D016601:RNA-Binding Proteins
keywords: ATG5; PDCD4; autophagy; proliferation; tumor suppressor