ArticleMolecular and cellular biology2014
Fbw7 targets GATA3 through cyclin-dependent kinase 2-dependent proteolysis and contributes to regulation of T-cell development.
Article in Molecular and cellular biology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed, 39 citations in OpenAlex.
- The Role of Ubiquitin-Proteasome System (UPS) in Asthma Pathology.Journal of asthma and allergy · 2025Review
- E3 ubiquitin ligase on the biological properties of hematopoietic stem cell.Journal of molecular medicine (Berlin, Germany) · 2023Review
- Expanded Potential Stem Cells from Human Embryos Have an Open Chromatin Configuration with Enhanced Trophoblast Differentiation Ability.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2023Article
- Systematic Discovery of FBXW7-Binding Phosphodegrons Highlights Mitogen-Activated Protein Kinases as Important Regulators of Intracellular Protein Levels.International journal of molecular sciences · 2022Article
- CDK1/FBXW7 facilitates degradation and ubiquitination of MLST8 to inhibit progression of renal cell carcinoma.Cancer science · 2022Article
- Protein ubiquitination in T cell development.Frontiers in immunology · 2022Review
- Recent Insight on Regulations of FBXW7 and Its Role in Immunotherapy.Frontiers in oncology · 2022Review
- Transcriptional Regulation of Early T-Lymphocyte Development in Thymus.Frontiers in immunology · 2022Review
- Post-Translational Modifications in Transcription Factors that Determine T Helper Cell Differentiation.Molecules and cells · 2021Review
- The role of aurora A and polo-like kinases in high-risk lymphomas.Blood advances · 2019Review
- Physiological functions of FBW7 in cancer and metabolism.Cellular signalling · 2018Review
- Cytokines, Transcription Factors, and the Initiation of T-Cell Development.Cold Spring Harbor perspectives in biology · 2018Review
- Participation of GATA-3 in regulation of bone healing through transcriptional upregulation of bcl-xExperimental & molecular medicine · 2017Article
- G-Protein Dependent Signal Transduction and Ubiquitination in Dictyostelium.International journal of molecular sciences · 2017Review
- Emerging role of DUBs in tumor metastasis and apoptosis: Therapeutic implication.Pharmacology & therapeutics · 2017Review
- Akt1-mediated Gata3 phosphorylation controls the repression of IFNγ in memory-type Th2 cells.Nature communications · 2016Article
- The emerging role of GATA transcription factors in development and disease.Expert reviews in molecular medicine · 2016Review
- Review
- Regulation of GATA-binding protein 2 levels via ubiquitin-dependent degradation by Fbw7: involvement of cyclin B-cyclin-dependent kinase 1-mediated phosphorylation of THR176 in GATA-binding protein 2.The Journal of biological chemistry · 2015Article
Corrections and comments
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Authors and funding
8 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Proper development of T cells depends on lineage-specific regulators controlled transcriptionally and posttranslationally to ensure precise levels at appropriate times. Conditional inactivation of F-box protein Fbw7 in mouse T-cell development resulted in reduced thymic CD4 single-positive (SP) and splenic CD4(+) and CD8(+) cell proportions. Fbw7 deficiency skewed CD8 SP lineage differentiation, which exhibited a higher incidence of apoptosis. Similar perturbations during development of CD8-positive cells were reported with transgenic mice, which enforced GATA3 (T-cell differentiation regulator) expression throughout T-cell development. We observed augmented GATA3 in CD4/CD8 double negative (DN) stage 4, CD4 SP, and CD8 SP lineages in Fbw7-deficient thymocytes. Using overexpressed proteins in cultured cells, we demonstrated that Fbw7 bound to, ubiquitylated, and destabilized GATA3. Two Cdc4 phosphodegron (CPD) candidate sequences, consensus Fbw7 recognition domains, were identified in GATA3, and phosphorylation of Thr-156 in CPD was required for Fbw7-mediated ubiquitylation and degradation. Phosphorylation of GATA3 Thr-156 was detected in mouse thymocytes, and cyclin-dependent kinase 2 (CDK2) was identified as a respondent for phosphorylation at Thr-156. These observations suggest that Fbw7-mediated GATA3 regulation with CDK2-mediated phosphorylation of CPD contributes to the precise differentiation of T-cell lineages.
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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.