دورية أكاديمية
أعرض في EDS

The parkin-coregulated gene product PACRG promotes TNF signaling by stabilizing LUBAC.

التفاصيل البيبلوغرافية
العنوان: The parkin-coregulated gene product PACRG promotes TNF signaling by stabilizing LUBAC.
المؤلفون: Meschede J; Molecular Cell Biology, Institute of Biochemistry and Pathobiochemistry, Ruhr University Bochum, 44801 Bochum, Germany., Šadić M; Neurobiochemistry, Adolf Butenandt Institute, Ludwig Maximilians University, 80336 Munich, Germany., Furthmann N; Molecular Cell Biology, Institute of Biochemistry and Pathobiochemistry, Ruhr University Bochum, 44801 Bochum, Germany., Miedema T; Molecular Cell Biology, Institute of Biochemistry and Pathobiochemistry, Ruhr University Bochum, 44801 Bochum, Germany., Sehr DA; Molecular Cell Biology, Institute of Biochemistry and Pathobiochemistry, Ruhr University Bochum, 44801 Bochum, Germany., Müller-Rischart AK; Neurobiochemistry, Adolf Butenandt Institute, Ludwig Maximilians University, 80336 Munich, Germany., Bader V; Molecular Cell Biology, Institute of Biochemistry and Pathobiochemistry, Ruhr University Bochum, 44801 Bochum, Germany., Berlemann LA; Molecular Cell Biology, Institute of Biochemistry and Pathobiochemistry, Ruhr University Bochum, 44801 Bochum, Germany., Pilsl A; Neurobiochemistry, Adolf Butenandt Institute, Ludwig Maximilians University, 80336 Munich, Germany., Schlierf A; Neurobiochemistry, Adolf Butenandt Institute, Ludwig Maximilians University, 80336 Munich, Germany., Barkovits K; Medizinisches Proteom-Center, Ruhr University Bochum, 44801 Bochum, Germany., Kachholz B; Molecular Cell Biology, Institute of Biochemistry and Pathobiochemistry, Ruhr University Bochum, 44801 Bochum, Germany., Rittinger K; The Francis Crick Institute, 1 Midland Road, London NW1 1AT, UK., Ikeda F; Institute of Molecular Biotechnology (IMBA), 1030 Vienna, Austria., Marcus K; Medizinisches Proteom-Center, Ruhr University Bochum, 44801 Bochum, Germany., Schaefer L; Pharmacenter Frankfurt/ZAFES, Institute for General Pharmacology and Toxicology, Goethe University, 60590 Frankfurt am Main, Germany., Tatzelt J; Neurobiochemistry, Adolf Butenandt Institute, Ludwig Maximilians University, 80336 Munich, Germany.; Biochemistry of Neurodegenerative Diseases, Institute of Biochemistry and Pathobiochemistry, Ruhr University Bochum, 44801 Bochum, Germany., Winklhofer KF; Molecular Cell Biology, Institute of Biochemistry and Pathobiochemistry, Ruhr University Bochum, 44801 Bochum, Germany. konstanze.winklhofer@rub.de.; Neurobiochemistry, Adolf Butenandt Institute, Ludwig Maximilians University, 80336 Munich, Germany.
المصدر: Science signaling [Sci Signal] 2020 Feb 04; Vol. 13 (617). Date of Electronic Publication: 2020 Feb 04.
نوع المنشور: Journal Article; Research Support, Non-U.S. Gov't
اللغة: English
بيانات الدورية: Publisher: American Association for the Advancement of Science Country of Publication: United States NLM ID: 101465400 Publication Model: Electronic Cited Medium: Internet ISSN: 1937-9145 (Electronic) Linking ISSN: 19450877 NLM ISO Abbreviation: Sci Signal Subsets: MEDLINE
أسماء مطبوعة: Original Publication: Washington, D.C. : American Association for the Advancement of Science
مواضيع طبية MeSH: Signal Transduction*, Microfilament Proteins/*metabolism , Molecular Chaperones/*metabolism , NF-kappa B/*metabolism , Tumor Necrosis Factor-alpha/*metabolism , Ubiquitin-Protein Ligases/*metabolism, Animals ; Cell Line, Tumor ; Cells, Cultured ; HEK293 Cells ; HeLa Cells ; Humans ; Mice, Knockout ; Microfilament Proteins/genetics ; Mitophagy/genetics ; Molecular Chaperones/genetics ; Nerve Tissue Proteins/genetics ; Nerve Tissue Proteins/metabolism ; Ubiquitin-Protein Ligases/genetics
مستخلص: The Parkin-coregulated gene ( PACRG ), which encodes a protein of unknown function, shares a bidirectional promoter with Parkin ( PRKN ), which encodes an E3 ubiquitin ligase. Because PRKN is important in mitochondrial quality control and protection against stress, we tested whether PACRG also affected these pathways in various cultured human cell lines and in mouse embryonic fibroblasts. PACRG did not play a role in mitophagy but did play a role in tumor necrosis factor (TNF) signaling. Similarly to Parkin, PACRG promoted nuclear factor κB (NF-κB) activation in response to TNF. TNF-induced nuclear translocation of the NF-κB subunit p65 and NF-κB-dependent transcription were decreased in PACRG-deficient cells. Defective canonical NF-κB activation in the absence of PACRG was accompanied by a decrease in linear ubiquitylation mediated by the linear ubiquitin chain assembly complex (LUBAC), which is composed of the two E3 ubiquitin ligases HOIP and HOIL-1L and the adaptor protein SHARPIN. Upon TNF stimulation, PACRG was recruited to the activated TNF receptor complex and interacted with LUBAC components. PACRG functionally replaced SHARPIN in this context. In SHARPIN-deficient cells, PACRG prevented LUBAC destabilization, restored HOIP-dependent linear ubiquitylation, and protected cells from TNF-induced apoptosis. This function of PACRG in positively regulating TNF signaling may help to explain the association of PACRG and PRKN polymorphisms with an increased susceptibility to intracellular pathogens.
(Copyright © 2020 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.)
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معلومات مُعتمدة: 094112 United Kingdom Wellcome Trust; FC001142 United Kingdom MRC_ Medical Research Council; FC001142 United Kingdom Wellcome Trust
المشرفين على المادة: 0 (Microfilament Proteins)
0 (Molecular Chaperones)
0 (NF-kappa B)
0 (Nerve Tissue Proteins)
0 (PACRG protein, human)
0 (Tumor Necrosis Factor-alpha)
0 (sharpin)
EC 2.3.2.27 (Ubiquitin-Protein Ligases)
تواريخ الأحداث: Date Created: 20200206 Date Completed: 20210201 Latest Revision: 20220129
رمز التحديث: 20221213
مُعرف محوري في PubMed: PMC7279956
DOI: 10.1126/scisignal.aav1256
PMID: 32019898
قاعدة البيانات: MEDLINE
الوصف
تدمد:1937-9145
DOI:10.1126/scisignal.aav1256