Phosphorylation of SWI/SNF chromatin remodeling component Brg1 and mechanisms involved in malignant transformation of cancer

2017 Fiscal Year Final Research Report

• Project/Area Number: 15K19028
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Pathological medical chemistry
• Research Institution: Yokohama City University
• Principal Investigator: KIMURA Ayuko 横浜市立大学, 先端医科学研究センター, 特任助教 (50553616)
• Project Period (FY): 2015-04-01 – 2018-03-31
• Keywords: リン酸化 / 癌 / 悪性化 / プロテオミクス / クロマチン再構成複合体

Outline of Final Research Achievements

The SWI/SNF complex contains many tumor suppressors (e.g., ARID1A and BRG1) that are frequently mutated in cancers including ovarian clear cell carcinoma (OCCC), a malignant subtype of ovarian cancers. Previously, we reported that the phosphorylation of BRG1 was significantly reduced in OCCC cells. To reveal the role of BRG1 phosphorylation, we analyzed the transcriptome, proteome, and phenotypes of cell lines with or without mutations in the phosphorylation site.
Proteome analysis revealed the upregulation of proteins and phosphoproteins involved in chromatin inactivation in phosphorylation-mimic mutant. In addition, the proliferative and migratory abilities of phosphorylation-mimic cells was decreased as compared to those of wild-type or phosphorylation-deleted cells. Transcriptome analysis also revealed their quantitative differences in genes involved in cell proliferation and migration, indicating the role of BRG1 phosphorylation in regulation of these genes.

Free Research Field

分子生物学、タンパク質化学