2015 Fiscal Year Final Research Report
Proteomic analysis of citrullinated targets regulated by the p53-PADI4 pathway
| Project/Area Number |
25710009
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| Research Category |
Grant-in-Aid for Young Scientists (A)
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| Allocation Type | Partial Multi-year Fund |
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| Research Field |
Tumor biology
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| Research Institution | The University of Tokyo |
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Principal Investigator |
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| Project Period (FY) |
2013-04-01 – 2016-03-31
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| Keywords | p53 / シトルリン化 |
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| Outline of Final Research Achievements |
Although recent proteome analyses have provided a comprehensive overview of various posttranscriptional modifications, the functions associated with protein citrullination remain unclear. Thus, we performed a proteomic screen and identified more than 100 PADI4 substrates associated with RNA processing and translation. Citrullination of RBMX inhibited the interaction with other hnRNP family members. RNA sequence analyses revealed that the splicing patterns of more than 300 genes were disrupted in bone marrow derived from Padi4-/- mice. Citrullination at the RGG motifs was elevated in a number of cancer tissues, and an antibody against citrullinated RGG motifs was observed in 17.5% of serum samples from patients with HCV-induced HCC. Our findings revealed that PADI4-mediated citrullination is associated with RNA processing and tumor immunogenicity and suggest that PADI4 activation has potential therapeutic implications for neurodegenerative disease treatment and cancer immunotherapy.
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| Free Research Field |
分子腫瘍学
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