The Protein Kinase C alpha regulates RIG-I mediated IRF3 activation through HDAC6 and beta-catenin (158.18)
| Autor: | Jianzhong Zhu, Saumendra Sarkar |
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| Rok vydání: | 2011 |
| Předmět: | |
| Zdroj: | The Journal of Immunology. 186:158.18-158.18 |
| ISSN: | 1550-6606 0022-1767 |
| DOI: | 10.4049/jimmunol.186.supp.158.18 |
| Popis: | RIG-I like receptors (RLR) are key cytoplasmic receptors to recognize viral RNA, and induce type I interferons via transcription factors such as IRF3 and NF-κB. Here we describe a novel signaling pathway involving PKCα, HDAC6 and β-catenin, which is essential for IRF3-mediated gene induction after virus infection. Stable knockdown of PKCα in various human cell lines inhibited Sendai virus-mediated IFN induction and enhanced virus replication. Sendai virus infection activated PKCα, which enhanced HDAC6 activity in a signal-dependent manner. HDAC6 physically interacted with PKCα and virus infection increased the deacetylation activity of HDAC6, which was absent in PKCα knockdown cells. HDAC6-mediated deacetylation of β-catenin enhanced its nuclear translocation and promoter binding, which was also attenuated in PKCα knockdown cells. We show that in the absence of PKCα/HDAC6-mediated β-catenin nuclear translocation, IRF3, although activated, does not bind to its promoter and is unable to support transcription. |
| Databáze: | OpenAIRE |
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