Functional analysis of BRCA genes and searching for molecular partner for synthetic lethality.
| Project/Area Number |
24300328
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (B)
|
| Allocation Type | Partial Multi-year Fund |
|---|
| Section | 一般 |
|---|
| Research Field |
Tumor biology
|
|---|
| Research Institution | Tokyo Medical and Dental University |
|---|
Principal Investigator |
MIKI Yoshio 東京医科歯科大学, 難治疾患研究所, 教授 (10281594)
|
|---|
| Co-Investigator(Kenkyū-buntansha) |
NAKANISHI Akira 東京医科歯科大学, 難治疾患研究所, 准教授 (50321790)
TAKENAKA Katsuya 東京医科歯科大学, 難治疾患研究所, 助教 (20378706)
|
|---|
| Project Period (FY) |
2012-04-01 – 2015-03-31
|
| Project Status |
Completed (Fiscal Year 2014)
|
| Budget Amount *help |
¥19,370,000 (Direct Cost: ¥14,900,000、Indirect Cost: ¥4,470,000)
Fiscal Year 2014: ¥5,590,000 (Direct Cost: ¥4,300,000、Indirect Cost: ¥1,290,000)
Fiscal Year 2013: ¥6,500,000 (Direct Cost: ¥5,000,000、Indirect Cost: ¥1,500,000)
Fiscal Year 2012: ¥7,280,000 (Direct Cost: ¥5,600,000、Indirect Cost: ¥1,680,000)
|
|---|
| Keywords | 乳がん / BRCA2 / 合成致死 / 化合物ライブラリー / BRCA1/2遺伝子 / がん抑制遺伝子 / BRCA1/BRCA2 / 抗がん剤 |
|---|
| Outline of Final Research Achievements |
We have reported the potential synthetic lethality relationships between BRCA2 deficiency and paclitaxel (PTX). To date, PTX treatment of BRCA2-siRNA knockdown cells has been found to result in a significant increase in microtubule polymer mass. To investigate whether the BRCA2 protein forms the microtubule cytoskeleton complex, we performed immunoprecipitation experiments using anti-BRCA2 antibody. Analysis of the immunoprecipitate by mass spectrometry identified the microtubule-associated proteins (MAP2, MAP4, and Tau) that directly bind microtubules to promote microtubule stabilization. Furthermore, a cell-based tubulin polymerization assay following the treatment of the siRNA knockdown of BRCA2 revealed microtubule stabilization by the effect of MAP4. In this study, we identified MAP4 as a new binding partner of BRCA2, suggesting that a synergistic effect of PTX and MAP4 on tubulin assembly contributes to microtubule stabilization.
|
Report
(4 results)
Research Products
(35 results)
-
-
-
-
-
-
[Journal Article]2013
Author(s)
Kawazu M, Ueno T, Kontani K, Ogita Y, Ando M, Fukumura K, Yamato A, Soda M, Takeuchi K, Miki Y, Yamaguchi H, Yasuda T, Naoe T,Yamashita Y, Katada T, Choi YL, Mano H,
-
Journal Title
Proc Natl Acad Sci U S A
Volume: 110
Issue: 8
Pages: 3029-3034
DOI
Related Report
Peer Reviewed
-
-
-
-
-
-
-
[Journal Article] Whole-exome sequencing of human pancreatic cancers and characterization of genomic instability caused by MLH1 haploinsufficiency and complete deficiency2012
Author(s)
Wang L, Tsutsumi S, Kawaguchi T,Nagasaki K, Tatsuno K, Yamamoto S, SangF, Sonoda K, Sugawara M, Saiura A,Hirono S, Yamaue H, Miki Y, Isomura M,Totoki Y, Nagae G, Isagawa T, Ueda H,Murayama-Hosokawa S, Shibata T,Sakamoto H, Kanai Y, Kaneda A, Noda T,Aburatani H
-
Journal Title
Genome Research
Volume: 22(2)
Issue: 2
Pages: 208-19
DOI
Related Report
Peer Reviewed
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
