Analysis of GATA4 dimarization during hypertrophic responses
Project/Area Number |
15K21279
|
Research Category |
Grant-in-Aid for Young Scientists (B)
|
Allocation Type | Multi-year Fund |
Research Field |
Biological pharmacy
Cardiovascular medicine
|
Research Institution | University of Shizuoka |
Principal Investigator |
|
Project Period (FY) |
2015-04-01 – 2018-03-31
|
Project Status |
Completed (Fiscal Year 2017)
|
Budget Amount *help |
¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000)
Fiscal Year 2017: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2016: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2015: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
|
Keywords | GATA4 / 心肥大反応 / 二量体形成 / 二量体化 / 結晶構造解析 / 転写因子 / 心肥大 / p300 / 二量体 |
Outline of Final Research Achievements |
A zinc finger protein, GATA4, associates with an intrinsic histone acetyltransferase (HAT), p300, and regulates myocardial transcriptional activities in response to hypertrophic stimuli. In this study, we demonstrated whether GATA4 formed a homo-dimer and its functional mechanism. Chemical cross-linking assay using nuclear extract from HEK293T cells showed that GATA4 homo-dimer was increased by co-expression of p300. IP-WB assay demonstrated that co-expression of GATA4 with p300 increased the formation of its homo-dimer as well as its acetylation. HAT-deficient mutant of p300 and acetyl-deficient mutant of GATA4 did not increase this homo-dimerization as well as GATA4-acetylation. These results suggest that acetylation of GATA4 is required for the formation of GATA4 dimerization. Thus, this dimerization may regulate hypertrophy-response gene activations and the development of heart failure.
|
Report
(4 results)
Research Products
(17 results)
-
[Presentation] Determination and crystallization of GATA4 dimerization domain spectrometry.2018
Author(s)
Shimizu S, Hara K, Sunagawa Y, Hishiki A, Miyazaki Y, Katanasaka Y, Funamoto M, Sari N, Shimizu K, Wada H, Hasegawa K, Hashimoto H, Morimoto T.
Organizer
IUBMB Focused Meeting on GATA Transcription Factors,
Related Report
Int'l Joint Research
-
-
[Presentation] Dimerization domain of GATA4, a hypertrophy-responsive transcription factor is the therapeutic targets2018
Author(s)
Shimizu S., Hara K, Sunagawa Y, Hishiki A, Funamoto M, Miyazaki Y, Katanasaka Y, Wada H, Hasegawa K, Hashimoto H, Morimoto T
Organizer
第1回日本循環器学会基礎研究フォーラム
Related Report
-
[Presentation] 心肥大応答を司る転写因子GATA4の二量体形成・DNA結合部位の同定と結晶化2018
Author(s)
清水聡史, 原幸大, 砂川陽一, 菱木麻美, 宮崎雄輔, 刀坂泰史, 船本雅文, Nurmila Sari, 清水果奈, 和田啓道, 長 谷川浩二, 橋本博, 森本達也
Organizer
日本 薬学会第138年会,
Related Report
-
[Presentation] The dimerization domain of the hypertrophy-responsive transcription factor GATA4 is a therapeutic target for heart failure2018
Author(s)
Shimizu S., Hara K, Sunagawa Y, Hishiki A, Funamoto M, Miyazaki Y, Katanasaka Y, Wada H, Hasegawa K, Hashimoto H, Morimoto T
Organizer
第82回日本循環器学会学術集会
Related Report
-
-
-
-
-
-
-
-
-
-
-
-