Clarification of action mechanism of caspase-activating molecules and cancer cell-selective induction of apoptosis

2014 Fiscal Year Final Research Report

• Project/Area Number: 24550189
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Chemistry related to living body
• Research Institution: Nara Institute of Science and Technology
• Principal Investigator: MATSUO Takashi 奈良先端科学技術大学院大学, 物質創成科学研究科, 准教授 (50432521)
• Co-Investigator(Renkei-kenkyūsha): HIROTA Shun 奈良先端科学技術大学院大学, 物質創成科学研究科, 教授 (90283457)
• Project Period (FY): 2012-04-01 – 2015-03-31
• Keywords: カスパーゼ / 有機小分子 / アポトーシス / 作用機構

Outline of Final Research Achievements

Caspase-3, a protease at the downstream of a apoptosis cascade, is produced from a zymogen protein (procaspase-3) with the help of other activator on cell stimuli. The activation process is inhibited in several kinds of cancerous cell because of much amounts of metal ions. This work focuses on the action mechanism of PAC-1, a compoound that recovers the activation process of procaspase-3 in cencerous cells, on the activities of (pro)caspase-3 from the viewpoint of enzymology. The kinetic studies of caspase-3 indicated that PAC-1 enhances the activity of mature caspase-3 as well as the recovery of activation process from the zymogen to mature form in the absence of metal ions. The effect of the compound on a mutant procaspase-3, a variant that has a weak caspase-3 activity, was found to be poor. In conclusion, PAC-1 has a structural perturbation mechanismis for affecting the (pro)caspase-3 activities as well as the metal ion-chelation removal pathway.

Free Research Field

生体機能関連化学