T-cell receptor (TCR) signaling promotes the assembly of RanBP2/RanGAP1-SUMO1/Ubc9 nuclear pore subcomplex via PKC-θ-mediated phosphorylation of RanGAP1
| Autor: | Chen-si Zhao, Yu Gong, Yujiao He, Amnon Altman, Dianying Feng, Yunting Du, Zhiguo Yang, Yiqi Chen, Yingqiu Li, Yun-Yi Li, Zhihui Xiao |
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| Rok vydání: | 2021 |
| Předmět: |
0301 basic medicine
Mouse SUMO protein t cell receptor Mice Immunology and Inflammation 0302 clinical medicine Biology (General) Nuclear pore phosphorylation Chemistry General Neuroscience GTPase-Activating Proteins General Medicine pkctheta Cell biology Medicine Phosphorylation Signal Transduction Research Article Human QH301-705.5 Science SUMO-1 Protein Receptors Antigen T-Cell rangap1 sumoylation nuclear transport macromolecular substances General Biochemistry Genetics and Molecular Biology 03 medical and health sciences nuclear pore complex otorhinolaryngologic diseases Animals Humans Protein kinase A Transcription factor General Immunology and Microbiology T-cell receptor Cell Biology Nuclear Pore Complex Proteins 030104 developmental biology Protein Kinase C-theta Ubiquitin-Conjugating Enzymes Nuclear Pore RANBP2 Nuclear transport 030217 neurology & neurosurgery Molecular Chaperones |
| Zdroj: | eLife, Vol 10 (2021) eLife |
| ISSN: | 2050-084X |
| DOI: | 10.7554/elife.67123 |
| Popis: | The nuclear pore complex (NPC) is the sole and selective gateway for nuclear transport, and its dysfunction has been associated with many diseases. The metazoan NPC subcomplex RanBP2, which consists of RanBP2 (Nup358), RanGAP1-SUMO1, and Ubc9, regulates the assembly and function of the NPC. The roles of immune signaling in regulation of NPC remain poorly understood. Here, we show that in human and murine T cells, following T-cell receptor (TCR) stimulation, protein kinase C-θ (PKC-θ) directly phosphorylates RanGAP1 to facilitate RanBP2 subcomplex assembly and nuclear import and, thus, the nuclear translocation of AP-1 transcription factor. Mechanistically, TCR stimulation induces the translocation of activated PKC-θ to the NPC, where it interacts with and phosphorylates RanGAP1 on Ser504 and Ser506. RanGAP1 phosphorylation increases its binding affinity for Ubc9, thereby promoting sumoylation of RanGAP1 and, finally, assembly of the RanBP2 subcomplex. Our findings reveal an unexpected role of PKC-θ as a direct regulator of nuclear import and uncover a phosphorylation-dependent sumoylation of RanGAP1, delineating a novel link between TCR signaling and assembly of the RanBP2 NPC subcomplex. |
| Databáze: | OpenAIRE |
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