ArticleInternational journal of molecular sciences2016
Human TRIB2 Oscillates during the Cell Cycle and Promotes Ubiquitination and Degradation of CDC25C.
Article in International journal of molecular sciences, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed, 23 citations in OpenAlex.
- Inducing TRIB2-targeted protein degradation to reverse chemoresistance in acute myeloid leukaemia.The Biochemical journal · 2026Article
- The Drosophila pseudokinase Tribbles translocates to the fat body membrane in response to fasting to modulate insulin sensitivity.Development (Cambridge, England) · 2025Article
- MGST1 Protects Pancreatic Ductal Cells from Inflammatory Damage in Acute Pancreatitis by Inhibiting Ferroptosis: Bioinformatics Analysis with Experimental Validation.International journal of molecular sciences · 2025Article
- Discovery of the first selective and potent PROTAC degrader for the pseudokinase TRIB2.European journal of medicinal chemistry · 2025Article
- TRIB1 confers therapeutic resistance in GBM cells by activating the ERK and Akt pathways.Scientific reports · 2023Article
- Review
- Tribbles homolog 2 (Trib2), a pseudo serine/threonine kinase in tumorigenesis and stem cell fate decisions.Cell communication and signaling : CCS · 2021Review
- Control of Cell Growth and Proliferation by the Tribbles Pseudokinase: Lessons from Drosophila.Cancers · 2021Review
- RFWD2 Knockdown as a Blocker to Reverse the Oncogenic Role of TRIB2 in Lung Adenocarcinoma.Frontiers in oncology · 2021Article
- Cataloguing the dead: breathing new life into pseudokinase research.The FEBS journal · 2020Review
- Covalent inhibitors of EGFR family protein kinases induce degradation of human Tribbles 2 (TRIB2) pseudokinase in cancer cells.Science signaling · 2018Article
- A Trib2-p38 axis controls myeloid leukaemia cell cycle and stress response signalling.Cell death & disease · 2018Article
- Trib2 expression in granulocyte-monocyte progenitors drives a highly drug resistant acute myeloid leukaemia linked to elevated Bcl2.Oncotarget · 2018Article
- ADisease models & mechanisms · 2017Article
- Tribbles in the 21st Century: The Evolving Roles of Tribbles Pseudokinases in Biology and Disease.Trends in cell biology · 2017Review
Corrections and comments
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Authors and funding
7 authors at 4 institutions in 2 countries.
Funding
Abstract
Tribbles homolog 2 (TRIB2) is a member of the mammalian Tribbles family of serine/threonine pseudokinases (TRIB1-3). Studies of TRIB2 indicate that many of the molecular interactions between the single Drosophila Tribbles (Trbl) protein and interacting partners are evolutionary conserved. In this study, we examined the relationship between TRIB2 and cell division cycle 25 (CDC25) family of dual-specificity protein phosphatases (mammalian homologues of Drosophila String), which are key physiological cell cycle regulators. Using co-immunoprecipitation we demonstrate that TRIB2 interacts with CDC25B and CDC25C selectively. Forced overexpression of TRIB2 caused a marked decrease in total CDC25C protein levels. Following inhibition of the proteasome, CDC25C was stabilized in the nuclear compartment. This implicates TRIB2 as a regulator of nuclear CDC25C turnover. In complementary ubiquitination assays, we show that TRIB2-mediated degradation of CDC25C is associated with lysine-48-linked CDC25C polyubiquitination driven by the TRIB2 kinase-like domain. A cell cycle associated role for TRIB2 is further supported by the cell cycle regulated expression of TRIB2 protein levels. Our findings reveal mitotic CDC25C as a new target of TRIB2 that is degraded via the ubiquitin proteasome system. Inappropriate CDC25C regulation could mechanistically underlie TRIB2 mediated regulation of cellular proliferation in neoplastic cells.
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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.