Investigation of JAK/STAT signalling and development of new reagents regulating JAK/STAT pathways
| Project/Area Number |
24590091
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (C)
|
| Allocation Type | Multi-year Fund |
|---|
| Section | 一般 |
|---|
| Research Field |
Biological pharmacy
|
|---|
| Research Institution | Keio University |
|---|
Principal Investigator |
|
|---|
| Co-Investigator(Kenkyū-buntansha) |
TAGO Megumi 慶應義塾大学, 薬学部, 准教授 (30445192)
|
|---|
| Project Period (FY) |
2012-04-01 – 2015-03-31
|
| Project Status |
Completed (Fiscal Year 2014)
|
| Budget Amount *help |
¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000)
Fiscal Year 2014: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2013: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2012: ¥2,600,000 (Direct Cost: ¥2,000,000、Indirect Cost: ¥600,000)
|
|---|
| Keywords | JAK/STATシグナル系 / JAK2 変異体 / c-Myc活性化 / オルニチンデカルボキシラーゼ / 抗がん剤耐性 / ファンコニタンパク質 / フラーレン誘導体 / JAK2シグナル解析 / 骨髄増殖性腫瘍 / V617F変異体 / STAT5の活性化 / c-Mycシグナル / ODC阻害剤 / MPN治療薬 / JAK2V617F / ODC / FANCC / 国際情報交換 |
|---|
| Outline of Final Research Achievements |
JAK2/STAT pathway is involved in many cytokine signaling of which mechanism still requires precise investigation. JAK2 V617F mutation is observed in majority of patients with myeloproliferative neoplasms (MPNs). We investigated how JAK2V617F mutation induces dysregulated proliferation and tumorigenesis. JAK2 V617F mutation induced significant c-Myc mRNA expression mediated by STAT5 activation, which induced subsequent ornithine decarboxylase (ODC). An ODC inhibitor prevented proliferation of JAK2V617F cells. Further, JAK2V617F exhibited resistance to anti-cancer drugs such as CDDP. We found that FANCC, a member of the Fanconi anemia (FA) proteins, is responsible to the resistance against the drug-induced DNA damage. In addition, pyrrolidinium fullerene markedly induced apoptosis of JAK2 V617F cells. These observations indicated that fullerene derivatives are suitable candidates inhibiting the JAK2 V617F-mediated proliferation and tumorigenesis.
|
Report
(4 results)
Research Products
(25 results)
-
-
-
[Journal Article] NLRP3 protein deficiency exacerbates hyperoxia-induced lethality through Stat3 protein signaling independent of interleukin-1β2015
Author(s)
Mizushina Y, Shirasuna K, Usui F, Karasawa T, Kawashima A, Kimura H, Kobayashi M, Komada T, Inoue Y, Mato N, Yamasawa H, Latz E, Iwakura Y, Kasahara T, Bando M, Sugiyama Y, Takahashi M
-
Journal Title
J Biol Chem
Volume: 290
Issue: 8
Pages: 5065-5077
DOI
Related Report
Peer Reviewed / Open Access
-
[Journal Article] Dietary deprivation of each essential amino acid induces differential systemic adaptive responses in mice.2014
Author(s)
Kamata S, Yamamoto J, Kamijo K, Ochiai T, Morita T, Yoshitomi Y, Hagiya Y, Kubota M, Ohkubo R, Kawaguchi M, Himi T, Kasahara T, Ishii I.
-
Journal Title
Mol Nutr Food Res.
Volume: 58
Issue: 6
Pages: 1309-1321
DOI
Related Report
Peer Reviewed / Open Access
-
-
-
-
-
-
-
-
[Presentation] 各必須アミノ酸欠失餌により異なるマウスの全身性適応応答2014
Author(s)
鎌田 祥太郎, 山本 隼也, 上條 健太, 落合 崇人, 森田 珠子, 吉冨 友里香, 萩谷 至史, 久保田 将史, 大久保 里佳, 笠原 忠, 石井 功
Organizer
第87回日本生化学会大会
Place of Presentation
京都市
Year and Date
2014-10-18
Related Report
-
-
-
-
-
-
-
-
-
-
-
-
-
