ArticleBlood2010
Transformation by Tribbles homolog 2 (Trib2) requires both the Trib2 kinase domain and COP1 binding.
Article in Blood, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 66 papers.
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Who cites it
66 citing papers in PubMed, 120 citations in OpenAlex.
- Inducing TRIB2-targeted protein degradation to reverse chemoresistance in acute myeloid leukaemia.The Biochemical journal · 2026Article
- TCF3 activates super-enhancer-driven TRIB2 overexpression to suppress ferroptosis and promote hepatoblastoma proliferation.Journal of experimental & clinical cancer research : CR · 2025Article
- Pseudokinase STK40 limits T cell exhaustion through COP1-dependent degradation of AP1-family transcription factors.Nature immunology · 2025Article
- COP1 Deficiency in BRAFCells · 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
- Rapid increase of C/EBPα p42 induces growth arrest of acute myeloid leukemia (AML) cells by Cop1 deletion in Trib1-expressing AML.Leukemia · 2024Article
- Wnt/β-catenin signaling regulates amino acid metabolism through the suppression of CEBPA and FOXA1 in liver cancer cells.Communications biology · 2024Article
- Article
- Mechanistic and evolutionary insights into isoform-specific 'supercharging' in DCLK family kinases.eLife · 2023Article
- Emerging functions of pseudoenzymes.The Biochemical journal · 2023Review
- Effect of COP1 in Promoting the Tumorigenesis of Gastric Cancer by Down-Regulation of CDH18 via PI3K/AKT Signal Pathway.Analytical cellular pathology (Amsterdam) · 2023Article
- Oncogenic TRIB2 interacts with and regulates PKM2 to promote aerobic glycolysis and lung cancer cell procession.Cell death discovery · 2022Article
- Article
- A methyltransferase-like 14/miR-99a-5p/tribble 2 positive feedback circuit promotes cancer stem cell persistence and radioresistance via histone deacetylase 2-mediated epigenetic modulation in esophageal squamous cell carcinoma.Clinical and translational medicine · 2021Article
- Tribbles pseudokinase NIPI-3 regulates intestinal immunity in Caenorhabditis elegans by controlling SKN-1/Nrf activity.Cell reports · 2021Article
- TRIB2 desensitizes ferroptosis via βTrCP-mediated TFRC ubiquitiantion in liver cancer cells.Cell death discovery · 2021Article
- Review
- SMURF1, a promoter of tumor cell progression?Cancer gene therapy · 2021Review
- Review
6 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
10 authors at 4 institutions in 1 country.
Funding
Abstract
Tribbles homolog 2 (Trib2) is a pseudokinase that induces acute myelogenous leukemia (AML) in mice and is highly expressed in a subset of human AML. Trib2 has 3 distinct regions, a proline-rich N-terminus, a serine/threonine kinase homology domain, and a C-terminal constitutive photomorphogenesis 1 (COP1)-binding domain. We performed a structure-function analysis of Trib2 using in vitro and in vivo assays. The N-terminus was not required for Trib2-induced AML. Deletion or mutation of the COP1-binding site abrogated the ability of Trib2 to degrade CCAAT/enhancer-binding protein-α (C/EBP-α), block granulocytic differentiation, and to induce AML in vivo. Furthermore, COP1 knockdown inhibited the ability of Trib2 to degrade C/EBP-α, showing that it is important for mediating Trib2 activity. We also show that the Trib2 kinase domain is essential for its function. Trib2 contains variant catalytic loop sequences, compared with conventional kinases, that we show are necessary for Trib2 activity. The kinase domain mutants bind, but cannot efficiently degrade, C/EBP-α. Together, our data demonstrate that Trib2 can bind both COP1 and C/EBP-α, leading to degradation of C/EBP-α. Identification of the functional regions of Trib2 that are essential to its oncogenic role provides the basis for developing inhibitors that will block Trib functions in cancer.
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What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.