تقرير
Control of GSK3β nuclear localization by amino acid signaling requires GATOR1 but is mTORC1-independent
| العنوان: | Control of GSK3β nuclear localization by amino acid signaling requires GATOR1 but is mTORC1-independent |
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| المؤلفون: | Diana Schwendener Forkel, Osemudiamen Ibazebo, Sumaiya Soha, Stephen J. Bautista, Stefania Impellizzeri, Roberto Botelho, Geoffrey Hesketh, Anne-Claude Gingras, Costin N. Antonescu |
| سنة النشر: | 2024 |
| مصطلحات موضوعية: | Organic chemistry, n.e.c, amino acids, GATOR1, GATOR2, nuclear localization |
| الوصف: | The availability of certain amino acids regulates cell survival, proliferation, growth, differentiation, and other cellular functions. Sensing of amino acids that converges on the GATOR1 and GATOR2 complexes supports activation of mTORC1 during amino acid replete conditions. Whether amino acid-derived cues regulate additional pathways remains poorly understood. We uncover that amino acid sensing involving GATOR1 and GATOR2 regulates the cellular localization of glycogen synthase kinase 3β (GSK3β). GATOR1 is required to recruit a subset of GSK3β to the lysosome selectively in the presence of amino acids. In addition, while under nutrient replete conditions GSK3β is largely cytosolic, amino acid starvation drives a portion of GSK3β into the nucleus. Acute replenishment of specific amino acids in starved cells triggered nuclear exit of GSK3β. This amino acid-stimulated GSKβ nuclear exit required GATOR1 and GATOR2 but was independent of mTORC1 and its activating RagA/B GTPases. This suggests that GATOR1 has a function that diverges from control of mTORC1 to regulate the nucleocytoplasmic shuttling of GSK3β. Furthermore, experimental restriction of GSK3β to the cytoplasm decreased cell survival in amino acid deficient conditions. This suggests that control of GSK3β nuclear localization by GATOR-dependent signals represents a cellular adaptation to metabolic stress that supports cell survival. |
| نوع الوثيقة: | report |
| اللغة: | unknown |
| العلاقة: | https://figshare.com/articles/preprint/Control_of_GSK3_nuclear_localization_by_amino_acid_signaling_requires_GATOR1_but_is_mTORC1-independent/26015170Test |
| DOI: | 10.32920/26015170.v1 |
| الإتاحة: | https://doi.org/10.32920/26015170.v1Test https://figshare.com/articles/preprint/Control_of_GSK3_nuclear_localization_by_amino_acid_signaling_requires_GATOR1_but_is_mTORC1-independent/26015170Test |
| حقوق: | CC BY-NC-ND 4.0 |
| رقم الانضمام: | edsbas.630C0E03 |
| قاعدة البيانات: | BASE |
| DOI: | 10.32920/26015170.v1 |
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