title: TGF-β upregulates the translation of USP15 via the PI3K/AKT pathway to promote p53 stability.
abstract: Crosstalk between transforming growth factor beta (TGF-β) signaling and p53 has a critical role in cancer progression. TGF-β signals via Smad and non-Smad pathways. Under normal conditions, wild-type p53 forms a complex with Smad2/3 and co-activates transcription of a variety of tumor suppressor genes, resulting in tumor suppressive effects. Thus, p53 stability is essential in progression of tumor suppressive responses mediated by TGF-β signaling. However, it remains unknown whether p53 stability is regulated by TGF-β. In the current study, we identify that USP15 binds to and stabilizes p53 through deubiquitination in U2OS and HEK293 cells. TGF-β promotes the translation of USP15 through activation of mammalian target of rapamycin by the phosphoinositide 3-kinase/AKT pathway. Upregulation of USP15 translation links the crosstalk between TGF-β signaling and p53 stability, allowing this cytokine to have a critical role in cancer progression.
authors.affiliation: Department of Life Science and Institute of Molecular Biology, National Chung Cheng University, Chia-Yi, Taiwan.
authors.forename: W-T
authors.initials: WT
authors.lastname: Liu
authors.affiliation: Department of Life Science and Institute of Molecular Biology, National Chung Cheng University, Chia-Yi, Taiwan.|Section of Allergy, Immunology and Rheumatology, Department of Medicine, DaLin Tzu-Chi Buddhist Hospital, Chia-Yi, Taiwan.|Department of Medicine, College of Medicine, Tzu-Chi University, Hualien, Taiwan.
authors.forename: K-Y
authors.initials: KY
authors.lastname: Huang
authors.affiliation: Section of Allergy, Immunology and Rheumatology, Department of Medicine, DaLin Tzu-Chi Buddhist Hospital, Chia-Yi, Taiwan.|Department of Medicine, College of Medicine, Tzu-Chi University, Hualien, Taiwan.
authors.forename: M-C
authors.initials: MC
authors.lastname: Lu
authors.affiliation: Department of Nutrition and Health Science, Fooyin University, Kaohsiung, Taiwan.
authors.forename: H-L
authors.initials: HL
authors.lastname: Huang
authors.affiliation: Department of Life Science and Institute of Molecular Biology, National Chung Cheng University, Chia-Yi, Taiwan.
authors.forename: C-Y
authors.initials: CY
authors.lastname: Chen
authors.affiliation: Department of Life Science and Institute of Molecular Biology, National Chung Cheng University, Chia-Yi, Taiwan.
authors.forename: Y-L
authors.initials: YL
authors.lastname: Cheng
authors.affiliation: Department of Life Science and Institute of Molecular Biology, National Chung Cheng University, Chia-Yi, Taiwan.|Section of Allergy, Immunology and Rheumatology, Department of Medicine, DaLin Tzu-Chi Buddhist Hospital, Chia-Yi, Taiwan.
authors.forename: H-C
authors.initials: HC
authors.lastname: Yu
authors.affiliation: Section of Allergy, Immunology and Rheumatology, Department of Medicine, DaLin Tzu-Chi Buddhist Hospital, Chia-Yi, Taiwan.
authors.forename: S-Q
authors.initials: SQ
authors.lastname: Liu
authors.affiliation: Section of Allergy, Immunology and Rheumatology, Department of Medicine, DaLin Tzu-Chi Buddhist Hospital, Chia-Yi, Taiwan.|Department of Medicine, College of Medicine, Tzu-Chi University, Hualien, Taiwan.
authors.forename: N-S
authors.initials: NS
authors.lastname: Lai
authors.affiliation: Department of Life Science and Institute of Molecular Biology, National Chung Cheng University, Chia-Yi, Taiwan.
authors.forename: H-B
authors.initials: HB
authors.lastname: Huang
mesh_terms: D017209:Apoptosis / Q000235:genetics; D049109:Cell Proliferation / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic; D057809:HEK293 Cells; D006801:Humans; D009369:Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D019869:Phosphatidylinositol 3-Kinases / Q000235:genetics; D011485:Protein Binding; D055550:Protein Stability; D051057:Proto-Oncogene Proteins c-akt / Q000235:genetics; D015398:Signal Transduction / Q000235:genetics; D051899:Smad2 Protein / Q000235:genetics / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000235:genetics* / Q000378:metabolism; D016159:Tumor Suppressor Protein p53 / Q000235:genetics* / Q000378:metabolism; D064570:Ubiquitin-Specific Proteases / Q000235:genetics* / Q000378:metabolism
chemical_list: C497782:SMAD2 protein, human; D051899:Smad2 Protein; C495901:TP53 protein, human; D016212:Transforming Growth Factor beta; D016159:Tumor Suppressor Protein p53; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt; C579226:USP15 protein, human; D064570:Ubiquitin-Specific Proteases