title: Ubiquitin E3 ligase SCF(β-TRCP) regulates TRIB2 stability in liver cancer cells.
abstract: Tribbles homolog 2 (TRIB2) is functionally important for liver cancer cell survival and transformation. Our previous study demonstrates TRIB2 is stable in liver cancer cells due to the impaired ubiquitination by Smurf1. However, overexpression of Smurf1 alone cannot completely abolish TRIB2 protein expression, whether other potential factors involved in the degradation of TRIB2 still remains unclear. In the present study, we reveal that the stability and ubiquitination of TRIB2 can also be controlled by ubiquitin E3 ligase SCF(β-TRCP). Depletion of either Cullin1 or β-TRCP up-regulates TRIB2 protein expression. Moreover, knockdown of β-TRCP extends the half-life, whereas reduces ubiquitylation of TRIB2. Similar to Smurf1, β-TRCP exerts its role through the TRIB2 Degradation Domain (TDD) at the N-terminus of the TRIB2 protein. Hence, we add TRIB2 to the substrate list of SCF(β-TRCP) and the finding may be helpful in the treatment of TRIB2 dependent liver cancer.
authors.affiliation: School of Public Health, Shanghai Jiaotong University, Shanghai 200025, China.
authors.forename: Yongxia
authors.initials: Y
authors.lastname: Qiao
authors.forename: Yue
authors.initials: Y
authors.lastname: Zhang
authors.forename: Jiayi
authors.initials: J
authors.lastname: Wang
mesh_terms: D017871:Calcium-Calmodulin-Dependent Protein Kinases; D045744:Cell Line, Tumor; D044842:Cullin Proteins / Q000235:genetics / Q000378:metabolism; D044783:F-Box Proteins / Q000235:genetics / Q000378:metabolism; D006706:Homeostasis; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism*; D008113:Liver Neoplasms / Q000201:enzymology*; D055550:Protein Stability; D044843:SKP Cullin F-Box Protein Ligases / Q000235:genetics / Q000378:metabolism*; D054875:Ubiquitination; D044844:beta-Transducin Repeat-Containing Proteins / Q000235:genetics / Q000378:metabolism
chemical_list: C100318:Cullin 1; D044842:Cullin Proteins; D044783:F-Box Proteins; D047908:Intracellular Signaling Peptides and Proteins; D044844:beta-Transducin Repeat-Containing Proteins; D044843:SKP Cullin F-Box Protein Ligases; D017871:Calcium-Calmodulin-Dependent Protein Kinases; C489044:TRIB2 protein, human
keywords: CHX; Cullin1; HCC; Hepatocellular carcinoma (HCC); IF; Protein stability; SCF complex; SKP1–cullin–F-box complex; TDD domain; TRIB2; TRIB2 degradation domain; Ubiquitination; beta-transducin repeat containing E3 ubiquitin protein ligase; cycloheximide; hepatocellular carcinoma; immunofluorescence; tribbles homolog 2; β-TRCP