Dokument: SIRT4 as a novel interactor and candidate suppressor of C-RAF kinase in MAPK signaling
| Titel: | SIRT4 as a novel interactor and candidate suppressor of C-RAF kinase in MAPK signaling | |||||||
| URL für Lesezeichen: | https://docserv.uni-duesseldorf.de/servlets/DocumentServlet?id=68361 | |||||||
| URN (NBN): | urn:nbn:de:hbz:061-20250130-122248-7 | |||||||
| Kollektion: | Publikationen | |||||||
| Sprache: | Englisch | |||||||
| Dokumententyp: | Wissenschaftliche Texte » Artikel, Aufsatz | |||||||
| Medientyp: | Text | |||||||
| Autoren: | Mehrabipour, Mehrnaz [Autor] Nakhaei-Rad, Saeideh [Autor] Dvorsky, Radovan [Autor] Lang, Alexander [Autor] Verhülsdonk, Patrick [Autor] Ahmadian, Mohammad Reza [Autor] Piekorz, Roland P. [Autor] | |||||||
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| Beschreibung: | Cellular responses leading to development, proliferation, and differentiation depend on RAF/MEK/ERK signaling, which integrates and amplifies signals from various stimuli for downstream cellular responses. C-RAF activation has been reported in many types of tumor cell proliferation and developmental disorders, necessitating the discovery of potential C-RAF protein regulators. Here, we identify a novel and specific protein interaction between C-RAF among the RAF kinase paralogs, and SIRT4 among the mitochondrial sirtuin family members SIRT3, SIRT4, and SIRT5. Structurally, C-RAF binds to SIRT4 through the N-terminal cysteine-rich domain, whereas SIRT4 predominantly requires the C-terminus for full interaction with C-RAF. Interestingly, SIRT4 specifically interacts with C-RAF in a pre-signaling inactive (serine 259–phosphorylated) state. Consistent with this finding, the expression of SIRT4 in HEK293 cells results in an up-regulation of pS259-C-RAF levels and a concomitant reduction in MAPK signaling as evidenced by strongly decreased phospho-ERK signals. Thus, we propose an additional extra-mitochondrial function of SIRT4 as a cytosolic tumor suppressor of C-RAF-MAPK signaling, besides its metabolic tumor suppressor role of glutamate dehydrogenase and glutamate levels in mitochondria. | |||||||
| Rechtliche Vermerke: | Originalveröffentlichung:
Mehrabipour, M., Nakhaei-Rad, S., Dvorsky, R., Lang, A., Verhülsdonk, P., Ahmadian, M. R., & Piekorz, R. P. (2024). SIRT4 as a novel interactor and candidate suppressor of C-RAF kinase in MAPK signaling. Life Science Alliance, 7(6), Article e202302507. https://doi.org/10.26508/lsa.202302507 | |||||||
| Lizenz: |  Dieses Werk ist lizenziert unter einer Creative Commons Namensnennung 4.0 International Lizenz | |||||||
| Fachbereich / Einrichtung: | Medizinische Fakultät | |||||||
| Dokument erstellt am: | 30.01.2025 | |||||||
| Dateien geändert am: | 30.01.2025 |
