ArticleThe Journal of biological chemistry2013
Impaired phosphorylation and ubiquitination by p70 S6 kinase (p70S6K) and Smad ubiquitination regulatory factor 1 (Smurf1) promote tribbles homolog 2 (TRIB2) stability and carcinogenic property in liver cancer.
Article in The Journal of biological chemistry, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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Who cites it
24 citing papers in PubMed, 48 citations in OpenAlex.
- Inducing TRIB2-targeted protein degradation to reverse chemoresistance in acute myeloid leukaemia.The Biochemical journal · 2026Article
- AMOTL2 inhibits lymph node metastasis in gastric cancer by suppressing TGF-β/Smad signaling and is destabilized by the E3 ubiquitin ligase SMURF1.International journal of biological sciences · 2026Article
- USP5 deubiquitinates and stabilizes IMPDH2, to promote hepatocellular carcinoma progression.Oncogene · 2025Article
- The Drosophila pseudokinase Tribbles translocates to the fat body membrane in response to fasting to modulate insulin sensitivity.Development (Cambridge, England) · 2025Article
- Discovery of the first selective and potent PROTAC degrader for the pseudokinase TRIB2.European journal of medicinal chemistry · 2025Article
- SNHG1: Redefining the Landscape of Hepatocellular Carcinoma through Long Noncoding RNAs.Biomedicines · 2024Review
- Decoding the Role of O-GlcNAcylation in Hepatocellular Carcinoma.Biomolecules · 2024Review
- Research Progress in Function and Regulation of E3 Ubiquitin Ligase SMURF1.Current medical science · 2023Review
- Regulation of TRIB1 abundance in hepatocyte models in response to proteasome inhibition.Scientific reports · 2023Article
- Oncogenic TRIB2 interacts with and regulates PKM2 to promote aerobic glycolysis and lung cancer cell procession.Cell death discovery · 2022Article
- Long noncoding RNA SNHG1 silencing accelerates hepatocyte-like cell differentiation of bone marrow-derived mesenchymal stem cells to alleviate cirrhosis via the microRNA-15a/SMURF1/UVRAG axis.Cell death discovery · 2022Article
- Comprehensive Profiling of Mammalian Tribbles Interactomes Implicates TRIB3 in Gene Repression.Cancers · 2021Article
- TRIB2 desensitizes ferroptosis via βTrCP-mediated TFRC ubiquitiantion in liver cancer cells.Cell death discovery · 2021Article
- SMURF1, a promoter of tumor cell progression?Cancer gene therapy · 2021Review
- Review
- Tribbles homolog 2 (Trib2), a pseudo serine/threonine kinase in tumorigenesis and stem cell fate decisions.Cell communication and signaling : CCS · 2021Review
- Use of signals of positive and negative selection to distinguish cancer genes and passenger genes.eLife · 2021Article
- TRIB2 modulates proteasome function to reduce ubiquitin stability and protect liver cancer cells against oxidative stress.Cell death & disease · 2021Article
- RFWD2 Knockdown as a Blocker to Reverse the Oncogenic Role of TRIB2 in Lung Adenocarcinoma.Frontiers in oncology · 2021Article
- Suppression of the Smurf1 Expression Inhibits Tumor Progression in Gliomas.Cellular and molecular neurobiology · 2018Article
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Authors and funding
9 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Tribbles homolog 2 (TRIB2) is critical for both solid and non-solid malignancies. Recently, TRIB2 was identified as a liver cancer-specific Wnt/β-catenin signaling downstream target and is functionally important for liver cancer cell survival and transformation. TRIB2 functions as a protein that interacts with E3 ubiquitin ligases and thereby modulates protein stability of downstream effectors. However, the regulation underlying TRIB2 protein stability per se has not yet been reported. In this study, we found that TRIB2 was up-regulated and exhibited high stability in liver cancer cells compared with other cells. We performed a structure-function analysis of TRIB2 and identified a domain (amino acids 1-5) at the N terminus that interacted with the E3 ubiquitin ligase Smurf1 and was critical for protein stability. Deletion of this domain extended TRIB2 half-life time accompanied with a more significant malignant property compared with wild type TRIB2. Furthermore, Smurf1-mediated ubiquitination required phosphorylation of TRIB2 by p70 S6 kinase (p70S6K) via another domain (amino acids 69-85) that is also essential for correct TRIB2 subcellular localization. Mutation of Ser-83 diminished p70S6K-induced phosphorylation of TRIB2. Moreover, the high stability of TRIB2 may be due to the fact that both p70S6K and Smurf1 were down-regulated and negatively correlated with TRIB2 expression in both liver cancer tissues and established liver cancer cell lines. Taken together, impaired phosphorylation and ubiquitination by p70S6K and Smurf1 increase the protein stability of TRIB2 in liver cancer and thus may be helpful in the development of diagnosis and treatment strategies against this malignant disease.
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