دورية أكاديمية
أعرض في EDS

Arginine methylation of caspase-8 controls life/death decisions in extrinsic apoptotic networks.

التفاصيل البيبلوغرافية
العنوان: Arginine methylation of caspase-8 controls life/death decisions in extrinsic apoptotic networks.
المؤلفون: Wohlfromm F; Translational Inflammation Research, Medical Faculty, Center of Dynamic Systems (CDS), Otto von Guericke University, 39106, Magdeburg, Germany., Ivanisenko NV; Translational Inflammation Research, Medical Faculty, Center of Dynamic Systems (CDS), Otto von Guericke University, 39106, Magdeburg, Germany., Pietkiewicz S; Translational Inflammation Research, Medical Faculty, Center of Dynamic Systems (CDS), Otto von Guericke University, 39106, Magdeburg, Germany., König C; Translational Inflammation Research, Medical Faculty, Center of Dynamic Systems (CDS), Otto von Guericke University, 39106, Magdeburg, Germany., Seyrek K; Translational Inflammation Research, Medical Faculty, Center of Dynamic Systems (CDS), Otto von Guericke University, 39106, Magdeburg, Germany., Kähne T; Institute of Experimental Internal Medicine, Medical Faculty, Otto von Guericke University, 39120, Magdeburg, Germany., Lavrik IN; Translational Inflammation Research, Medical Faculty, Center of Dynamic Systems (CDS), Otto von Guericke University, 39106, Magdeburg, Germany. inna.lavrik@med.ovgu.de.
المصدر: Oncogene [Oncogene] 2024 Jun; Vol. 43 (25), pp. 1955-1971. Date of Electronic Publication: 2024 May 10.
نوع المنشور: Journal Article
اللغة: English
بيانات الدورية: Publisher: Nature Publishing Group Country of Publication: England NLM ID: 8711562 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1476-5594 (Electronic) Linking ISSN: 09509232 NLM ISO Abbreviation: Oncogene Subsets: MEDLINE
أسماء مطبوعة: Publication: <2002->: Basingstoke : Nature Publishing Group
Original Publication: Basingstoke, Hampshire, UK : Scientific & Medical Division, MacMillan Press, c1987-
مواضيع طبية MeSH: Caspase 8*/metabolism , Caspase 8*/genetics , Arginine*/metabolism , Apoptosis* , Protein-Arginine N-Methyltransferases*/metabolism , Protein-Arginine N-Methyltransferases*/genetics, Humans ; Methylation ; Protein Processing, Post-Translational
مستخلص: Procaspase-8 is a key mediator of death receptor (DR)-mediated pathways. Recently, the role of post-translational modifications (PTMs) of procaspase-8 in controlling cell death has received increasing attention. Here, using mass spectrometry screening, pharmacological inhibition and biochemical assays, we show that procaspase-8 can be targeted by the PRMT5/RIOK1/WD45 methylosome complex. Furthermore, two potential methylation sites of PRMT5 on procaspase-8, R233 and R435, were identified in silico. R233 and R435 are highly conserved in mammals and their point mutations are among the most common mutations of caspase-8 in cancer. The introduction of mutations at these positions resulted in inhibitory effects on CD95L-induced caspase-8 activity, effector caspase activation and apoptosis. In addition, we show that procaspase-8 can undergo symmetric di-methylation. Finally, the pharmacological inhibition of PRMT5 resulted in the inhibitory effects on caspase activity and apoptotic cell death. Taken together, we have unraveled the additional control checkpoint in procaspase-8 activation and the arginine methylation network in the extrinsic apoptosis pathway.
(© 2024. The Author(s).)
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معلومات مُعتمدة: 2017.008.02 Wilhelm Sander-Stiftung (Wilhelm Sander Foundation); LA 2386 Deutsche Forschungsgemeinschaft (German Research Foundation)
المشرفين على المادة: EC 3.4.22.- (Caspase 8)
94ZLA3W45F (Arginine)
EC 2.1.1.319 (Protein-Arginine N-Methyltransferases)
EC 2.1.1.319 (PRMT5 protein, human)
EC 3.4.22.- (CASP8 protein, human)
تواريخ الأحداث: Date Created: 20240510 Date Completed: 20240614 Latest Revision: 20240627
رمز التحديث: 20240627
مُعرف محوري في PubMed: PMC11178496
DOI: 10.1038/s41388-024-03049-6
PMID: 38730267
قاعدة البيانات: MEDLINE
الوصف
تدمد:1476-5594
DOI:10.1038/s41388-024-03049-6