Acetylation-dependent glutamate receptor GluR signalosome formation for STAT3 activation in both transcriptional and metabolism regulation
| Autor: | Xiaju Cheng, Jia Sun, Chao Huang, Yimei Hao, Xiang-rong Li, Nannan Chen, Yan S. Xu, Y. Eugene Chin |
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| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
0301 basic medicine
Cancer Research Immunology lcsh:RC254-282 Article 03 medical and health sciences Cellular and Molecular Neuroscience 0302 clinical medicine lcsh:QH573-671 STAT3 biology Chemistry lcsh:Cytology Glutamate receptor Acetylation Cell Biology lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens Cell biology CNS cancer 030104 developmental biology Metabotropic glutamate receptor Acetyltransferase biology.protein STAT protein Signal transduction 030217 neurology & neurosurgery Ionotropic effect |
| Zdroj: | Cell Death Discovery, Vol 7, Iss 1, Pp 1-11 (2021) Cell Death Discovery |
| ISSN: | 2058-7716 |
| Popis: | Besides their original regulating roles in the brain, spinal cord, retina, and peripheral nervous system for mediating fast excitatory synaptic transmission, glutamate receptors consisting of metabotropic glutamate receptors (GluRs) and ionotropic glutamate receptors (iGluRs) have emerged to have a critical role in the biology of cancer initiation, progression, and metastasis. However, the precise mechanism underpinning the signal transduction mediated by ligand-bound GluRs is not clearly elucidated. Here, we show that iGluRs, GluR1 and GluR2, are acetylated by acetyltransferase CREB-binding protein upon glutamate stimulation of cells, and are targeted by lysyl oxidase-like 2 for deacetylation. Acetylated GluR1/2 recruit β-arrestin1/2 and signal transducer and activator of transcription 3 (STAT3) to form a protein complex. Both β-arrestin1/2 and STAT3 are subsequently acetylated and activated. Simultaneously, activated STAT3 acetylated at lysine 685 translocates to mitochondria to upregulate energy metabolism-related gene transcription. Our results reveal that acetylation-dependent formation of GluR1/2–β-arrestin1/2–STAT3 signalosome is critical for glutamate-induced cell proliferation. |
| Databáze: | OpenAIRE |
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