title: STAT3 Potentiates SIAH-1 Mediated Proteasomal Degradation of β-Catenin in Human Embryonic Kidney Cells.
abstract: The β-catenin functions as an adhesion molecule and a component of the Wnt signaling pathway. In the absence of the Wnt ligand, β-catenin is constantly phosphorylated, which designates it for degradation by the APC complex. This process is one of the key regulatory mechanisms of β-catenin. The level of β-catenin is also controlled by the E3 ubiquitin protein ligase SIAH-1 via a phosphorylation-independent degradation pathway. Similar to β-catenin, STAT3 is responsible for various cellular processes, such as survival, proliferation, and differentiation. However, little is known about how these molecules work together to regulate diverse cellular processes. In this study, we investigated the regulatory relationship between STAT3 and β-catenin in HEK293T cells. To our knowledge, this is the first study to report that β-catenin-TCF-4 transcriptional activity was suppressed by phosphorylated STAT3; furthermore, STAT3 inactivation abolished this effect and elevated activated β-catenin levels. STAT3 also showed a strong interaction with SIAH-1, a regulator of active β-catenin via degradation, which stabilized SIAH-1 and increased its interaction with β-catenin. These results suggest that activated STAT3 regulates active β-catenin protein levels via stabilization of SIAH-1 and the subsequent ubiquitin-dependent proteasomal degradation of β-catenin in HEK293T cells.
authors.affiliation: Department of Pharmacology, Seoul National University College of Medicine, Seoul 03080, Korea.|Department of Biomedical Sciences, Seoul National University College of Medicine, Seoul 03080, Korea.
authors.forename: Minkyung
authors.initials: M
authors.lastname: Shin
authors.affiliation: Department of Pharmacology, Seoul National University College of Medicine, Seoul 03080, Korea.|Department of Biomedical Sciences, Seoul National University College of Medicine, Seoul 03080, Korea.|Ischemic/Hypoxic Disease Institute, Seoul National University College of Medicine, Seoul 03080, Korea.
authors.forename: Eun Hee
authors.initials: EH
authors.lastname: Yi
authors.affiliation: Department of Pharmacology, Seoul National University College of Medicine, Seoul 03080, Korea.|Brain Korea 21 Plus (BK21 ), Seoul National University College of Medicine, Seoul 03080, Korea.
authors.forename: Byung-Hak
authors.initials: BH
authors.lastname: Kim
authors.affiliation: Pohang Center for Evaluation of Biomaterials, Pohang 37673, Korea.
authors.forename: Jae-Cheon
authors.initials: JC
authors.lastname: Shin
authors.affiliation: Industry-Academic Cooperation Foundation, Hanbat National University, Daejeon 34158, Korea.
authors.forename: Jung Youl
authors.initials: JY
authors.lastname: Park
authors.affiliation: Department of Pharmacology, Seoul National University College of Medicine, Seoul 03080, Korea.|Department of Biomedical Sciences, Seoul National University College of Medicine, Seoul 03080, Korea.|Ischemic/Hypoxic Disease Institute, Seoul National University College of Medicine, Seoul 03080, Korea.
authors.forename: Chung-Hyun
authors.initials: CH
authors.lastname: Cho
authors.affiliation: Department of Pharmacology, Seoul National University College of Medicine, Seoul 03080, Korea.|Department of Biomedical Sciences, Seoul National University College of Medicine, Seoul 03080, Korea.|Ischemic/Hypoxic Disease Institute, Seoul National University College of Medicine, Seoul 03080, Korea.
authors.forename: Jong-Wan
authors.initials: JW
authors.lastname: Park
authors.affiliation: Department of Biotechnology, College of Life Science and Biotechnology, Yonsei University, Seoul 09722, Korea.
authors.forename: Kang-Yell
authors.initials: KY
authors.lastname: Choi
authors.affiliation: Department of Pharmacology, Seoul National University College of Medicine, Seoul 03080, Korea.|Department of Biomedical Sciences, Seoul National University College of Medicine, Seoul 03080, Korea.|Ischemic/Hypoxic Disease Institute, Seoul National University College of Medicine, Seoul 03080, Korea.
authors.forename: Sang-Kyu
authors.initials: SK
authors.lastname: Ye
mesh_terms: D051778:Basic Helix-Loop-Helix Leucine Zipper Transcription Factors / Q000235:genetics / Q000378:metabolism; D057809:HEK293 Cells; D006801:Humans; D007668:Kidney / Q000166:cytology / Q000196:embryology / Q000378:metabolism; D009687:Nuclear Proteins / Q000378:metabolism*; D010766:Phosphorylation; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism*; D050796:STAT3 Transcription Factor / Q000235:genetics / Q000378:metabolism*; D000073940:Transcription Factor 4; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D014158:Transcription, Genetic; D014162:Transfection; D044767:Ubiquitin-Protein Ligases / Q000378:metabolism*; D051176:beta Catenin / Q000235:genetics / Q000378:metabolism*; D000098563:Seven in Absentia Proteins
chemical_list: D051778:Basic Helix-Loop-Helix Leucine Zipper Transcription Factors; C495270:CTNNB1 protein, human; D009687:Nuclear Proteins; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; C532096:TCF4 protein, human; D000073940:Transcription Factor 4; D014157:Transcription Factors; D051176:beta Catenin; D044767:Ubiquitin-Protein Ligases; D000098563:Seven in Absentia Proteins; D046988:Proteasome Endopeptidase Complex
keywords: SIAH-1; STAT3; proteasomal degradation; β-catenin