ArticleThe Journal of biological chemistry2012
Coordinated regulation of transcription factor Bcl11b activity in thymocytes by the mitogen-activated protein kinase (MAPK) pathways and protein sumoylation.
Article in The Journal of biological chemistry, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 papers.
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Who cites it
39 citing papers in PubMed, 63 citations in OpenAlex.
- Bcl11b dose-dependently regulates positive selection of CD8 T cells to the virtual memory fate.bioRxiv : the preprint server for biology · 2026Article
- Bipartite DNA binding domain of transcription factor BCL11B binds clustered short DNA sequence motifs.bioRxiv : the preprint server for biology · 2026Article
- SUMOylation modulates the dual functions of Krüppel homolog 1 in transcriptional regulation of Broad-Complex expression.Journal of advanced research · 2025Article
- Targeting BCL11B in CAR-engineered lymphoid progenitors drives NK-like cell development with prolonged anti-leukemic activity.Molecular therapy : the journal of the American Society of Gene Therapy · 2025Article
- The emerging roles of ubiquitin-like modifications in regulating HIV replication and host defense.Frontiers in cellular and infection microbiology · 2025Review
- Transcriptional network dynamics in early T cell development.The Journal of experimental medicine · 2024Review
- The function of BCL11B in base excision repair contributes to its dual role as an oncogene and a haplo-insufficient tumor suppressor gene.Nucleic acids research · 2024Article
- The Antimicrobial Peptide Cathelicidin Exerts Immunomodulatory Effects via Scavenger Receptors.International journal of molecular sciences · 2023Article
- Computational study of SENP1 in cancer by novel natural compounds and ZINC database screening.Frontiers in pharmacology · 2023Article
- SUMOylation targeting mitophagy in cardiovascular diseases.Journal of molecular medicine (Berlin, Germany) · 2022Review
- SUMOylation and Viral Infections of the Brain.Pathogens (Basel, Switzerland) · 2022Review
- BCL11B depletion induces the development of highly cytotoxic innate T cells out of IL-15 stimulated peripheral blood αβ CD8+ T cells.Oncoimmunology · 2022Article
- Unveiling the N-Terminal Homodimerization of BCL11B by Hybrid Solvent Replica-Exchange Simulations.International journal of molecular sciences · 2021Article
- SUMO and Transcriptional Regulation: The Lessons of Large-Scale Proteomic, Modifomic and Genomic Studies.Molecules (Basel, Switzerland) · 2021Review
- Interplay between cofactors and transcription factors in hematopoiesis and hematological malignancies.Signal transduction and targeted therapy · 2021Review
- Epigenetic Dynamics in the Function of T-Lineage Regulatory Factor Bcl11b.Frontiers in immunology · 2021Review
- Targeting the Transcriptome Through Globally Acting Components.Frontiers in genetics · 2021Review
- Bcl11b/Ctip2 in Skin, Tooth, and Craniofacial System.Frontiers in cell and developmental biology · 2020Review
- Aberrant calcium channel splicing drives defects in cortical differentiation in Timothy syndrome.eLife · 2019Article
- Human Cortical Organoids Expose a Differential Function of GSK3 on Cortical Neurogenesis.Stem cell reports · 2019Article
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Authors and funding
8 authors at 1 institution in 1 country.
Funding
Abstract
The transcriptional regulatory protein Bcl11b is essential for T-cell development. We have discovered a dynamic, MAPK-regulated pathway involving sequential, linked, and reversible post-translational modifications of Bcl11b in thymocytes. MAPK-mediated phosphorylation of Bcl11b was coupled to its rapid desumoylation, which was followed by a subsequent cycle of dephosphorylation and resumoylation. Additionally and notably, we report the first instance of direct identification by mass spectrometry of a site of small ubiquitin-like modifier (SUMO) adduction, Lys-679 of Bcl11b, in a protein isolated from a native, mammalian cell. Sumoylation of Bcl11b resulted in recruitment of the transcriptional co-activator p300 to a Bcl11b-repressed promoter with subsequent induction of transcription. Prolonged treatment of native thymocytes with phorbol 12,13-dibutyrate together with the calcium ionophore A23187 also promoted ubiquitination and proteasomal degradation of Bcl11b, providing a mechanism for signal termination. A Bcl11b phospho-deSUMO switch was identified, the basis of which was phosphorylation-dependent recruitment of the SUMO hydrolase SENP1 to phospho-Bcl11b, coupled to hydrolysis of SUMO-Bcl11b. These results define a regulatory pathway in thymocytes that includes the MAPK pathways and upstream signaling components, Bcl11b and the associated nucleosome remodeling and deacetylation (NuRD) complex, SENP proteins, the Bcl11b protein phosphatase 6, the sumoylation machinery, the histone acetyltransferase p300, and downstream transcriptional machinery. This pathway appears to facilitate derepression of repressed Bcl11b target genes as immature thymocytes initiate differentiation programs, biochemically linking MAPK signaling with the latter stages of T-cell development.
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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.