2020 Fiscal Year Final Research Report
GANP may reulates the c-Myc expression in germinal center (GCs), that is essential for the affinity maturation of B cells)
| Project/Area Number |
19K16691
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| Research Category |
Grant-in-Aid for Early-Career Scientists
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| Allocation Type | Multi-year Fund |
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| Review Section |
Basic Section 49070:Immunology-related
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| Research Institution | Osaka University |
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Principal Investigator |
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| Project Period (FY) |
2019-04-01 – 2021-03-31
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| Keywords | GANP / c-Myc / eIF4E |
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| Outline of Final Research Achievements |
Germinal Center (GC)-associated nuclear protein (GANP) was discovered as up-regulated molecule in GC B cells upon T cell dependent immune responses, GANP-deficient mice failed to generate affinity-maturation of Ag-specific antibodies in B cells thus; GANP is critical molecule for the regulation of adaptive immune system.
We investigated mRNAs and proteins associated with GANP in B cells. GANP interacts with many kinds of RNAs for various functions of cancer development, cell cycling, DNA repair, and protein translation. GANP interacts with the translation initiation factor eIF4E and efficiently targets the transcription factor c-Myc mRNA. Furthermore, GANP regulates c-Myc translation via interacting with the 5’ untranslated region of c-Myc mRNA in B cells. The results indicated that GANP is necessary for the upregulation of c-Myc in B cells undergoing the selection process in the GCs. The augmented c-Myc expression by GANP is likely a regulatory signal for B cell positive selection.
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| Free Research Field |
Immune Regulations
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| Academic Significance and Societal Importance of the Research Achievements |
Our studies suggest that GANP regulates the c-Myc mRNA in cooperation with translation initiation factor eIF4E, for the positive selection of high affinity GC B cells during immune responses. Our research direction holds great promise for the discovery of new targets for therapeutic applications.
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