Ubc9 Interacts with and SUMOylates the TCR Adaptor SLP-76 for NFAT Transcription in T Cells
| Autor: | Yan Wang, Yiwei Xiong, Yulan Yi, Hebin Liu, Naiqi Yang, Christopher E. Rudd |
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| Rok vydání: | 2019 |
| Předmět: |
genetic structures
T cell T-Lymphocytes Immunology SUMO protein Receptors Antigen T-Cell SH2 domain Jurkat cells Jurkat Cells Mice medicine Immunology and Allergy Animals Humans Cells Cultured Adaptor Proteins Signal Transducing NFATC Transcription Factors Chemistry T-cell receptor Signal transducing adaptor protein Sumoylation NFAT equipment and supplies Phosphoproteins eye diseases Cell biology medicine.anatomical_structure HEK293 Cells Phosphoprotein Ubiquitin-Conjugating Enzymes sense organs |
| Zdroj: | Journal of immunology (Baltimore, Md. : 1950). 203(11) |
| ISSN: | 1550-6606 |
| Popis: | Although the immune adaptor SH2 domain containing leukocyte phosphoprotein of 76 kDa (SLP-76) integrates and propagates the TCR signaling, the regulation of SLP-76 during the TCR signaling is incompletely studied. In this article, we report that SLP-76 interacts with the small ubiquitin-like modifier (SUMO) E2 conjugase Ubc9 and is a substrate for Ubc9-mediated SUMOylation in human and mouse T cells. TCR stimulation promotes SLP-76–Ubc9 binding, accompanied by an increase in SLP-76 SUMOylation. Ubc9 binds to the extreme C terminus of SLP-76 spanning residues 516–533 and SUMOylates SLP-76 at two conserved residues K266 and K284. In addition, SLP-76 and Ubc9 synergizes to augment the TCR-mediated IL-2 transcription by NFAT in a manner dependent of SUMOylation of SLP-76. Moreover, although not affecting the TCR proximal signaling events, the Ubc9-mediated SUMOylation of SLP-76 is required for TCR-induced assembly of Ubc9-NFAT complex for IL-2 transcription. Together, these results suggest that Ubc9 modulates the function of SLP-76 in T cell activation both by direct interaction and by SUMOylation of SLP-76 and that the Ubc9–SLP-76 module acts as a novel regulatory complex in the control of T cell activation. |
| Databáze: | OpenAIRE |
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