title: TRIB2 inhibits Wnt/β-Catenin/TCF4 signaling through its associated ubiquitin E3 ligases, β-TrCP, COP1 and Smurf1, in liver cancer cells.
abstract: Tribbles homolog 2 (TRIB2) is specifically regulated by Wnt signaling in liver cancer cells but not in colon cancer cells. However, whether and how TRIB2 regulates Wnt signaling in liver cancer cells remains unclear. Here, we report that TRIB2 negatively regulates Wnt activity through a reduction in protein stability of TCF4 and β-Catenin. Mechanistically, TRIB2 associated-ubiquitin E3 ligases beta-transducin repeat-containing E3 ubiquitin protein ligase (β-TrCP), COP1 and Smad ubiquitination regulatory factor 1 (Smurf1) reduced TCF4/β-Catenin expression, and these effects could be enhanced by TRIB2. Moreover, deletion of the binding regions of these E3-ligases within the TRIB2 protein decreased ubiquitination of TCF4/β-Catenin and reduced nuclear accumulation of β-TrCP, COP1 and Smurf1, which suggested that TRIB2 regulated-Wnt activity is closely correlated with its associated E3 ligases.
authors.affiliation: Department of Clinical Laboratory Medicine, Shanghai Tenth People's Hospital of Tongji University, 200072 Shanghai, China.
authors.forename: Shanshan
authors.initials: S
authors.lastname: Xu
authors.affiliation: Department of Clinical Laboratory Medicine, Tong Ren Hospital Affiliated to Shanghai Jiaotong University School of Medicine, 200336 Shanghai, China.
authors.forename: Minghong
authors.initials: M
authors.lastname: Tong
authors.affiliation: Department of Clinical Laboratory Medicine, Shanghai Tenth People's Hospital of Tongji University, 200072 Shanghai, China.
authors.forename: Jingqin
authors.initials: J
authors.lastname: Huang
authors.affiliation: Department of Central Laboratory, Shanghai Tenth People's Hospital of Tongji University, China.
authors.forename: Yue
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: School of Public Health, Shanghai Jiaotong University School of Medicine, Shanghai 200025, China.
authors.forename: Yongxia
authors.initials: Y
authors.lastname: Qiao
authors.affiliation: Department of Clinical Laboratory Medicine, Shanghai Tenth People's Hospital of Tongji University, 200072 Shanghai, China.
authors.forename: Wenhao
authors.initials: W
authors.lastname: Weng
authors.affiliation: Department of Clinical Laboratory Medicine, Shanghai Tenth People's Hospital of Tongji University, 200072 Shanghai, China.
authors.forename: Weiwei
authors.initials: W
authors.lastname: Liu
authors.affiliation: Department of Clinical Laboratory Medicine, Shanghai Tenth People's Hospital of Tongji University, 200072 Shanghai, China. Electronic address: karajan2@163.com.
authors.forename: Jiayi
authors.initials: J
authors.lastname: Wang
authors.affiliation: Department of Clinical Laboratory Medicine, Shanghai Tenth People's Hospital of Tongji University, 200072 Shanghai, China. Electronic address: sunfenyong@126.com.
authors.forename: Fenyong
authors.initials: F
authors.lastname: Sun
mesh_terms: D021581:Active Transport, Cell Nucleus; D051778:Basic Helix-Loop-Helix Leucine Zipper Transcription Factors / Q000737:chemistry / Q000378:metabolism; D001665:Binding Sites; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D045744:Cell Line, Tumor; D002467:Cell Nucleus / Q000378:metabolism; D015536:Down-Regulation; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism*; D008113:Liver Neoplasms / Q000473:pathology*; D055550:Protein Stability; D000073940:Transcription Factor 4; D014157:Transcription Factors / Q000737:chemistry / Q000378:metabolism; D044767:Ubiquitin-Protein Ligases / Q000378:metabolism*; D054875:Ubiquitination; D060449:Wnt Signaling Pathway; D051176:beta Catenin / Q000737:chemistry / Q000378:metabolism; D044844:beta-Transducin Repeat-Containing Proteins / Q000378:metabolism*
chemical_list: D051778:Basic Helix-Loop-Helix Leucine Zipper Transcription Factors; D047908:Intracellular Signaling Peptides and Proteins; C532096:TCF4 protein, human; D000073940:Transcription Factor 4; D014157:Transcription Factors; D051176:beta Catenin; D044844:beta-Transducin Repeat-Containing Proteins; C498342:SMURF1 protein, human; C471981:COP1 protein, human; D044767:Ubiquitin-Protein Ligases; D017871:Calcium-Calmodulin-Dependent Protein Kinases; C489044:TRIB2 protein, human
keywords: Liver cancer; Protein stability; Ubiquitination; Wnt/β-Catenin signaling