2016 Fiscal Year Final Research Report
Functional analysis of LUBAC in the inhibition of cell death and the activation in B cells.
| Project/Area Number |
26460573
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Immunology
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| Research Institution | Kyoto University |
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Principal Investigator |
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| Project Period (FY) |
2014-04-01 – 2017-03-31
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| Keywords | 免疫学 / ユビキチン / 細胞死 / B細胞 / シグナル伝達 |
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| Outline of Final Research Achievements |
Linear polyubiquitin chains are generated specifically by the ubiquitin ligase complex LUBAC. LUBAC is composed of one catalytic subunit, HOIP and two accessary subunits, HOIL-1L and SHARPIN. In this study I analyzed the role of LUBAC in TLR4-mediated cell death of B cells lacking LUBAC activity. I found that among two signal transduces downstream of TLR4, MyD88 and TRIF TRIF is responsible for this cell death because ablation of TRIF prevented TLR4-induced cell death of HOIP deficient B cells. I also discovered that deletion of RIP3, a critical regulator of necroptosis alone did not inhibit TLR4-induced cell death but the inhibition of Caspase-8 together with RIP3 deletion restored LPS-induced survival and cell proliferation of HOIP deficient B cells. These data show that LUBAC plays critical roles in the inhibition of Caspase-mediated apoptosis induced by TLR4 stimulation.
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| Free Research Field |
免疫学
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