The three dimensional structure study of p53 mutants by using microscopic laser raman spectroscopy aimed at developing a non-invasive cancer diagnostic system

Research Project

Project/Area Number	25670569
Research Category	Grant-in-Aid for Challenging Exploratory Research
Allocation Type	Multi-year Fund
Research Field	Digestive surgery
Research Institution	The University of Tokyo
Principal Investigator	SETO Yasuyuki 東京大学, 医学部附属病院, 教授 (00260498)
Project Period (FY)	2013-04-01 – 2015-03-31
Project Status	Completed (Fiscal Year 2014)
Budget Amount *help	¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000) Fiscal Year 2014: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000) Fiscal Year 2013: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Keywords	癌抑制遺伝子p53 / 蛋白質 / 変異 / 高次構造 / 顕微レーザーラマン分光 / 分子動力学シミュレーション / p53
Outline of Final Research Achievements	Cancer is caused by DNA changes within cells. p53 is called the guardian of the genome, because it plays a key role in preventing the changes . About half of p53 in human cancers is either lost or mutated, which results in losing the function. The study aimed to observe how p53 mutants lose p53 original function by using microscopic laser raman spectroscopy. Raman spectroscopy is an analytical technique to observe scattered photons from a laser beam into the molecules. The frequency of the scattered photons has information on vibrational motions of atoms in molecules and is sensitive to molecular conformation and environment. The spectroscopy can be applied to in-vivo observation. p53 normal proteins have one zinc ion. We observed that the scattered photons attributed to Zn disappear in the spectra of mutants near the zinc binding site, and that loss of zinc induces the disruption of the normal structure .