ArticleCell death & disease2021
TRIB2 modulates proteasome function to reduce ubiquitin stability and protect liver cancer cells against oxidative stress.
Article in Cell death & disease, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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Who cites it
26 citing papers in PubMed, 37 citations in OpenAlex.
- Inducing TRIB2-targeted protein degradation to reverse chemoresistance in acute myeloid leukaemia.The Biochemical journal · 2026Article
- LZTR1 Loss Reduces Vimentin Expression and Motility in Hep3B Hepatocellular Carcinoma Cells.International journal of molecular sciences · 2026Article
- Multidimensional exploration of the relationship between gut microbiota and colorectal cancer: focus on clinical tumorigenesis and treatment.Frontiers in immunology · 2026Review
- PCBP2 in gastrointestinal cancers: fundamental mechanism and clinical potential.Journal of molecular medicine (Berlin, Germany) · 2025Review
- Acteoside ameliorates hepatocyte ferroptosis and hepatic ischemia-reperfusion injuryActa pharmaceutica Sinica. B · 2025Article
- The role of tribbles homolog 2 in cell proliferation.Cell communication and signaling : CCS · 2025Review
- Research progress of ferroptosis pathway and its related molecular ubiquitination modification in liver cancer.Frontiers in oncology · 2025Review
- TRIM32 promotes neuronal ferroptosis by enhancing K63-linked ubiquitination and subsequent p62-selective autophagic degradation of GPX4.International journal of biological sciences · 2025Article
- Overexpression of long noncoding RNA DUXAP8 inhibits ER-phagy through activating AKT/mTOR signaling and contributes to preeclampsia.Cellular and molecular life sciences : CMLS · 2024Article
- Decoding the Role of O-GlcNAcylation in Hepatocellular Carcinoma.Biomolecules · 2024Review
- Activation of hepatic adenosine A1 receptor ameliorates MASH via inhibiting SREBPs maturation.Cell reports. Medicine · 2024Article
- Suppression of A-to-I RNA-editing enzyme ADAR1 sensitizes hepatocellular carcinoma cells to oxidative stress through regulating Keap1/Nrf2 pathway.Experimental hematology & oncology · 2024Article
- Ferroptosis in liver cancer: a key role of post-translational modifications.Frontiers in immunology · 2024Review
- Targeting epigenetic and posttranslational modifications regulating ferroptosis for the treatment of diseases.Signal transduction and targeted therapy · 2023Review
- Development and validation of a ubiquitin-proteasome system gene signature for prognostic prediction and immune microenvironment evaluation in hepatocellular carcinoma.Journal of cancer research and clinical oncology · 2023Article
- TRIB1 regulates liver regeneration by antagonizing the NRF2-mediated antioxidant response.Cell death & disease · 2023Article
- Common Pathogenetic Mechanisms Underlying Aging and Tumor and Means of Interventions.Aging and disease · 2022Article
- Essential roles of exosome and circRNA_101093 on ferroptosis desensitization in lung adenocarcinoma.Cancer communications (London, England) · 2022Article
- YAP ISGylation increases its stability and promotes its positive regulation on PPP by stimulating 6PGL transcription.Cell death discovery · 2022Article
- Anti-Anemic Effect of Antioxidant-Rich Apple Vinegar against Phenylhydrazine-Induced Hemolytic Anemia in Rats.Life (Basel, Switzerland) · 2022Article
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Authors and funding
8 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The regulation of homeostasis in the Ubiquitin (Ub) proteasome system (UPS) is likely to be important for the development of liver cancer. Tribbles homolog 2 (TRIB2) is known to affect Ub E3 ligases (E3s) in liver cancer. However, whether TRIB2 regulates the UPS in other ways and the relevant mechanisms are still unknown. Here, we reveal that TRIB2 decreased Ub levels largely by stimulating proteasome degradation of Ub. In the proteasome, proteasome 20S subunit beta 5 (PSMB5) was critical for the function of TRIB2, although it did not directly interact with TRIB2. However, poly (rC) binding protein 2 (PCBP2), which was identified by mass spectrometry, directly interacted with both TRIB2 and PSMB5. PCBP2 was a prerequisite for the TRIB2 induction of PSMB5 activity and decreased Ub levels. A significant correlation between TRIB2 and PCBP2 was revealed in liver cancer specimens. Interestingly, TRIB2 suppressed the K48-ubiquitination of PCBP2 to increase its level. Therefore, a model showing that TRIB2 cooperates and stimulates PCBP2 to reduce Ub levels was established. Additionally, the reduction in Ub levels induced by TRIB2 and PCBP2 was dependent on K48-ubiquitination. PCBP2 was one of the possible downstream factors of TRIB2 and their interaction relied on the DQLVPD element of TRIB2 and the KH3 domain of PCBP2. This interaction was necessary to maintain the viability of the liver cancer cells and promote tumor growth. Mechanistically, glutathione peroxidase 4 functioned as one of the terminal effectors of TRIB2 and PCBP2 to protect liver cancer cells from oxidative damage. Taken together, the data indicate that, in addition to affecting E3s, TRIB2 plays a critical role in regulating UPS by modulating PSMB5 activity in proteasome to reduce Ub flux, and that targeting TRIB2 might be helpful in liver cancer treatments by enhancing the oxidative damage induced by therapeutic agents.
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