دورية أكاديمية
APEX2-Mediated Proximity Labeling Resolves the DDIT4-Interacting Proteome
| العنوان: | APEX2-Mediated Proximity Labeling Resolves the DDIT4-Interacting Proteome |
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| المؤلفون: | Marianna Naki, Olga Gourdomichali, Katerina Zonke, Fedon-Giasin Kattan, Manousos Makridakis, Georgia Kontostathi, Antonia Vlahou, Epaminondas Doxakis |
| المصدر: | International Journal of Molecular Sciences, Vol 23, Iss 9, p 5189 (2022) |
| بيانات النشر: | MDPI AG, 2022. |
| سنة النشر: | 2022 |
| المجموعة: | LCC:Biology (General) LCC:Chemistry |
| مصطلحات موضوعية: | DDIT4, APEX2, proximity labeling, interactome, proteomics, LC-MS/MS, Biology (General), QH301-705.5, Chemistry, QD1-999 |
| الوصف: | DNA damage-inducible transcript 4 (DDIT4) is a ubiquitous protein whose expression is transiently increased in response to various stressors. Chronic expression has been linked to various pathologies, including neurodegeneration, inflammation, and cancer. DDIT4 is best recognized for repressing mTORC1, an essential protein complex activated by nutrients and hormones. Accordingly, DDIT4 regulates metabolism, oxidative stress, hypoxic survival, and apoptosis. Despite these well-defined biological functions, little is known about its interacting partners and their unique molecular functions. Here, fusing an enhanced ascorbate peroxidase 2 (APEX2) biotin-labeling enzyme to DDIT4 combined with mass spectrometry, the proteins in the immediate vicinity of DDIT4 in either unstressed or acute stress conditions were identified in situ. The context-dependent interacting proteomes were quantitatively but not functionally distinct. DDIT4 had twice the number of interaction partners during acute stress compared to unstressed conditions, and while the two protein lists had minimal overlap in terms of identity, the proteins’ molecular function and classification were essentially identical. Moonlighting keratins and ribosomal proteins dominated the proteomes in both unstressed and stressed conditions, with many of their members having established non-canonical and indispensable roles during stress. Multiple keratins regulate mTORC1 signaling via the recruitment of 14-3-3 proteins, whereas ribosomal proteins control translation, cell cycle progression, DNA repair, and death by sequestering critical proteins. In summary, two potentially distinct mechanisms of DDIT4 molecular function have been identified, paving the way for additional research to confirm and consolidate these findings. |
| نوع الوثيقة: | article |
| وصف الملف: | electronic resource |
| اللغة: | English |
| تدمد: | 1422-0067 1661-6596 |
| العلاقة: | https://www.mdpi.com/1422-0067/23/9/5189Test; https://doaj.org/toc/1661-6596Test; https://doaj.org/toc/1422-0067Test |
| DOI: | 10.3390/ijms23095189 |
| الوصول الحر: | https://doaj.org/article/337fded1e5044862b1d38dd00985a3b1Test |
| رقم الانضمام: | edsdoj.337fded1e5044862b1d38dd00985a3b1 |
| قاعدة البيانات: | Directory of Open Access Journals |
Full Text Finder | تدمد: | 14220067 16616596 |
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| DOI: | 10.3390/ijms23095189 |