Ubiquitin E3 ligase SCF(β-TRCP) regulates TRIB2 stability in liver cancer cells

Biochem Biophys Res Commun. 2013 Nov 22;441(3):555-9. doi: 10.1016/j.bbrc.2013.10.123. Epub 2013 Nov 5.

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.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Calcium-Calmodulin-Dependent Protein Kinases
  • Cell Line, Tumor
  • Cullin Proteins / genetics
  • Cullin Proteins / metabolism
  • F-Box Proteins / genetics
  • F-Box Proteins / metabolism
  • Homeostasis
  • Humans
  • Intracellular Signaling Peptides and Proteins / genetics
  • Intracellular Signaling Peptides and Proteins / metabolism*
  • Liver Neoplasms / enzymology*
  • Protein Stability
  • SKP Cullin F-Box Protein Ligases / genetics
  • SKP Cullin F-Box Protein Ligases / metabolism*
  • Ubiquitination
  • beta-Transducin Repeat-Containing Proteins / genetics
  • beta-Transducin Repeat-Containing Proteins / metabolism

Substances

  • Cullin 1
  • Cullin Proteins
  • F-Box Proteins
  • Intracellular Signaling Peptides and Proteins
  • beta-Transducin Repeat-Containing Proteins
  • SKP Cullin F-Box Protein Ligases
  • Calcium-Calmodulin-Dependent Protein Kinases
  • TRIB2 protein, human