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2015 Fiscal Year Final Research Report

Proteomic analysis of citrullinated targets regulated by the p53-PADI4 pathway

Research Project

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Project/Area Number 25710009
Research Category

Grant-in-Aid for Young Scientists (A)

Allocation TypePartial Multi-year Fund
Research Field Tumor biology
Research InstitutionThe University of Tokyo

Principal Investigator

Tanikawa Chizu  東京大学, 医科学研究所, 助教 (30422421)

Project Period (FY) 2013-04-01 – 2016-03-31
Keywordsp53 / シトルリン化
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.

Free Research Field

分子腫瘍学

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Published: 2017-05-10  

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