Efficient cardiac induction of embryionic stem cells and induced pluripotent stem cells through regulation of ubiquitin-proteasome pathway.

2014 Fiscal Year Final Research Report

• Project/Area Number: 24591105
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Circulatory organs internal medicine
• Research Institution: National Cardiovascular Center Research Institute
• Principal Investigator: ASAKURA Masanori 独立行政法人国立循環器病研究センター, 研究開発基盤センター, 室長 (80443505)
• Co-Investigator(Kenkyū-buntansha): KITAKAZE Masafumi 国立循環器病研究センター, 研究開発基盤センター, 部長 (20294069)
• Research Collaborator: MIN Kyung-Duk
• Project Period (FY): 2012-04-01 – 2015-03-31
• Keywords: 心筋分化 / ユビキチン / プロテアソーム系

Outline of Final Research Achievements

Heart failure is one of the leading causes of death in Japan and the novel diagnosis and treatment are strongly awaited. To overcome this issue, we aimed to elucidate the molecular mechanisms of cardiac induction in embryonic stem cells (ES cells). Comprehensive gene expression analysis using ES cells identified Asb2, which is thought to be an E3 ligase. Further analysis revealed that Asb2 is specifically expressed in the heart and skeletal muscle during development. In silico data base suggested potential interaction between Asb2 and Smad9, and we confirmed that Asb2 is the E3 ligase for Smad9 and leads it to proteasomal degradation. Our data suggested that Asb2-dependent Smad9 degradation plays important role in the development of the heart through quantitative regulation of Smad9 and thus the regulation of BMP signaling.

Free Research Field

循環器内科学