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Inducible expression and phosphorylation of coactivator BOB.1/OBF.1 in T cells
S Zwilling1, A Dieckmann, P Pfisterer
1MSZ, Institut für Medizinische Strahlenkunde und Zellforschung, Universität Würzburg, Versbacher Strasse 5, 97078 Würzburg, Germany.
Summary
The transcriptional coactivator BOB.1/OBF.1 is regulated by phosphorylation at Ser184. This modification is crucial for its function in both T and B cells, enabling cell-type-specific gene expression.
Area of Science:
- Molecular Biology
- Immunology
- Gene Regulation
Background:
- BOB.1/OBF.1 is a transcriptional coactivator constitutively expressed in B cells.
- It interacts with Oct1 and Oct2 transcription factors, key regulators in B cell development and function.
Purpose of the Study:
- To investigate the regulation of BOB.1/OBF.1 activity.
- To determine the role of posttranslational modifications, specifically phosphorylation, in BOB.1/OBF.1 function.
- To elucidate the cell type-specific mechanisms of BOB.1/OBF.1-mediated gene expression.
Main Methods:
- Analysis of BOB.1/OBF.1 expression and transactivation function in activated Jurkat T cells and murine thymocytes.
- In vivo and in vitro phosphorylation studies of BOB.1/OBF.1 at Ser184.
- Site-directed mutagenesis of Ser184 to assess its impact on transactivation in both T and B cells.
Main Results:
- BOB.1/OBF.1 expression and transactivation function were induced upon activation of T cells.
- Phosphorylation at Ser184 was identified as a critical modification for inducible T cell activation.
- Mutation of Ser184 impaired transactivation in B cells, indicating constitutive phosphorylation in these cells.
Conclusions:
- BOB.1/OBF.1 is a key transcriptional coactivator regulated by phosphorylation.
- Posttranslational modification at Ser184 is essential for both inducible T cell activation and constitutive B cell function.
- These findings highlight the role of phosphorylation in mediating cell type-specific gene expression by BOB.1/OBF.1.