title: Proteasome inhibitors and knockdown of SMG1 cause accumulation of Upf1 and Upf2 in human cells.
abstract: The ubiquitin-proteasome system (UPS) is one of the most promising anticancer drug targets of the century. However, the involved molecular mechanisms are still unclear. The nonsense-mediated mRNA decay (NMD) pathway is a highly conserved pathway which degrades nonsense mutation‑containing mRNA selectively and efficiently. In this pathway, the SMG1-Upf1-eRF (SURF) complex binds to Upf2 on the exon junction complex and finally causes degradation of nonsense-containing mRNA. To reveal the relationship between the UPS and NMD pathways, we analyzed the effects of proteasome inhibitors on Upf1 and Upf2. The data showed that treatment with proteasome inhibitors caused the accumulation of the Upf1 and Upf2 proteins in A549 cells. In addition, we found that knockdown of SMG1 also caused the upregulation of Upf1 and Upf2 proteins, which was confirmed by different target sequences of siRNA. SMG1 and UPS appear to participate in different pathways of the degradation of Upf1 and Upf2, since simultaneous treatment with both of them caused additive effects. This study demonstrated the quantitative regulation of Upf1 and Upf2 proteins by UPS and SMG1.
authors.affiliation: Institute of Pathology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, P.R. China.
authors.forename: Xia
authors.initials: X
authors.lastname: Zhao
authors.forename: Atsushi
authors.initials: A
authors.lastname: Nogawa
authors.forename: Tsukasa
authors.initials: T
authors.lastname: Matsunaga
authors.forename: Tsutomu
authors.initials: T
authors.lastname: Takegami
authors.forename: Hideaki
authors.initials: H
authors.lastname: Nakagawa
authors.forename: Yasuhito
authors.initials: Y
authors.lastname: Ishigaki
mesh_terms: D000111:Acetylcysteine / Q000031:analogs & derivatives / Q000494:pharmacology; D000730:Androstadienes / Q000494:pharmacology; D003513:Cycloheximide / Q000494:pharmacology; D005091:Exons; D015972:Gene Expression Regulation, Neoplastic; D055785:Gene Knockdown Techniques; D006801:Humans; D059365:Nonsense Mediated mRNA Decay / Q000187:drug effects / Q000235:genetics; D019869:Phosphatidylinositol 3-Kinases / Q000235:genetics*; D010766:Phosphorylation / Q000187:drug effects; D061988:Proteasome Inhibitors / Q000494:pharmacology*; D017346:Protein Serine-Threonine Kinases; D020365:RNA Helicases; D034741:RNA, Small Interfering / Q000235:genetics; D016601:RNA-Binding Proteins; D015534:Trans-Activators / Q000096:biosynthesis* / Q000235:genetics; D014157:Transcription Factors / Q000096:biosynthesis* / Q000235:genetics; D025801:Ubiquitin / Q000378:metabolism; D000077191:Wortmannin
chemical_list: D000111:Acetylcysteine; D000730:Androstadienes; D003513:Cycloheximide; D019869:Phosphatidylinositol 3-Kinases; D061988:Proteasome Inhibitors; D017346:Protein Serine-Threonine Kinases; D020365:RNA Helicases; D034741:RNA, Small Interfering; D016601:RNA-Binding Proteins; D015534:Trans-Activators; D014157:Transcription Factors; D025801:Ubiquitin; D000077191:Wortmannin; C468286:UPF2 protein, human; C067713:lactacystin; C514704:SMG1 protein, human; C101828:UPF1 protein, human