2022 Fiscal Year Final Research Report
Clarification of the molecular mechanism of NF-kB regulation by novel family of linear ubiquitin binding protein
| Project/Area Number |
20K06611
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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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| Review Section |
Basic Section 43060:System genome science-related
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| Research Institution | Ehime University |
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Principal Investigator |
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| Project Period (FY) |
2020-04-01 – 2023-03-31
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| Keywords | ユビキチン結合タンパク質 / ZFAND / 直鎖ユビキチン鎖 / NF-kB |
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| Outline of Final Research Achievements |
In protein ubiquitination process, eight kinds of polyubiquitin chains are formed by conjugation of one ubiquitin molecule to another ubiquitin that binds to target proteins. The functions and roles of individual polyubiquitin chains are mainly decided by ubiquitin binding proteins (UBPs). In this study, we attempted to clarify the roles of novel M1-UBPs belonging to ZFAND family, which has been identified in our previous study, in a signal transduction of NF-kB activation. Our results strongly suggested that ZFAND5 that showed high binding activity with M1-ubiquitin chain suppressed the NF-kB signaling by acting with proteins that are subjected with K63- and M1-polyubiquitination. Interestingly, this suppression was proceeded in concert with other UBPs.
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| Free Research Field |
シグナル伝達
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| Academic Significance and Societal Importance of the Research Achievements |
NF-kBシグナル伝達経路は細胞の炎症や免疫、生存を左右する非常に重要な経路であり、これまでに多くの研究が成されている。しかし、個々の細胞イベントによって、使われる因子やそのアウトプットとして起こる細胞応答は複雑多岐にわたっており、まだ未詳な点が少なくない。本研究において、これまで機能未知だったZFANDファミリーに焦点を絞り、その機能の一端の解明に成功した。これらの結果から、NF-kB活性化時に形成されるユビキチン鎖に、ZFAND5をはじめとするUBPが数多く集結し、その活性を制御していることが示唆されており、上記の炎症や免疫のイベントに寄与することが示唆された。
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