التفاصيل البيبلوغرافية
| العنوان: |
PP6 negatively modulates LUBAC-mediated M1-ubiquitination of RIPK1 and c-FLIPL to promote TNFα-mediated cell death |
| المؤلفون: |
Guowei Wu, Dekang Li, Wei Liang, Weimin Sun, Xingxing Xie, Yilun Tong, Bing Shan, Mengmeng Zhang, Xiaojuan Lu, Junying Yuan, Ying Li |
| المصدر: |
Cell Death and Disease, Vol 13, Iss 9, Pp 1-14 (2022) |
| بيانات النشر: |
Nature Publishing Group, 2022. |
| سنة النشر: |
2022 |
| المجموعة: |
LCC:Cytology |
| مصطلحات موضوعية: |
Cytology, QH573-671 |
| الوصف: |
Abstract Activation of TNFR1 by TNFα induces the formation of a membrane-associated, intracellular complex termed complex I. Complex I orchestrates a complex pattern of modifications on key regulators of TNF signaling that collectively determines the cell fate by activating pro-survival or executing cell death programs. However, the regulatory mechanism of complex I in cell-fate decision is not fully understood. Here we identify protein phosphatase-6 (PP6) as a previously unidentified component of complex I. Loss of PP6 protects cells from TNFα-mediated cell death. The role of PP6 in regulating cell death requires its phosphatase activity and regulatory subunits. Further mechanistic studies show that PP6 modulates LUBAC-mediated M1-ubiquitination of RIPK1 and c-FLIPL to promote RIPK1 activation and c-FLIPL degradation. We also show that melanoma-associated PP6 inactivating mutants offer resistance to cell death due to the loss of sensitivity to TNFα. Thus, our study provides a potential mechanism by which melanoma-related PP6 inactivating mutations promote cancer progression. |
| نوع الوثيقة: |
article |
| وصف الملف: |
electronic resource |
| اللغة: |
English |
| تدمد: |
2041-4889 |
| Relation: |
https://doaj.org/toc/2041-4889 |
| DOI: |
10.1038/s41419-022-05206-9 |
| URL الوصول: |
https://doaj.org/article/b0e40f33ed404a358026112134298f31 |
| رقم الانضمام: |
edsdoj.b0e40f33ed404a358026112134298f31 |
| قاعدة البيانات: |
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