Analysis of androgen-mediated p53 regulatory mechanism at transcriptional and protein levels
| Project/Area Number |
15K15581
|
|---|
| Research Category |
Grant-in-Aid for Challenging Exploratory Research
|
| Allocation Type | Multi-year Fund |
|---|
| Research Field |
Urology
|
|---|
| Research Institution | Tokyo Metropolitan Geriatric Hospital and Institute of Gerontology (2016-2017)
The University of Tokyo (2015) |
|---|
Principal Investigator |
Takayama Ken-ichi 地方独立行政法人東京都健康長寿医療センター(東京都健康長寿医療センター研究所), 東京都健康長寿医療センター研究所, 研究員 (50508075)
|
|---|
| Project Period (FY) |
2015-04-01 – 2018-03-31
|
| Project Status |
Completed (Fiscal Year 2017)
|
| Budget Amount *help |
¥3,510,000 (Direct Cost: ¥2,700,000、Indirect Cost: ¥810,000)
Fiscal Year 2016: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2015: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
|
|---|
| Keywords | Prostate / p53 / Androgen / Nuclear export / G3BP2 / TRIM25 / USP10 / アンドロゲン受容体 / 前立腺癌 / ホルモン / 翻訳後修飾 / アンドロゲン / 転写制御 |
|---|
| Outline of Final Research Achievements |
The androgen receptor (AR) has a central role in prostate cancer progression. Loss of the p53 tumor suppressor contributes to malignancy. We identified G3BP2 as a novel AR target involved in p53 signals by integrative sequence analysis. We then explored how G3BP2 modulates p53 activity and revealed that RanBP2, SUMO-E3 ligase, and TRIM25 are promising G3BP2-associating proteins in addition to known USP10. Mechanistically, translocation of p53 to cytoplasm was promoted by androgen-dependent sumoylation mediated by RanBP2. TRIM25 was indispensable for this complex formation and translocation of p53 to cytoplasm. Furthermore, G3BP2 expression is regulated at protein level through USP10-mediated inhibition of G3BP2 polyubiquitylation. Thus, G3BP2 has a repressive effect on p53 signaling through systematic interaction with RanBP2/TRIM25/USP10.
|
Report
(4 results)
Research Products
(41 results)
-
-
-
-
-
-
-
-
-
-
-
-
-
-
[Journal Article] A novel prognostic factor TRIM44 promotes cell proliferation and migration, and inhibits apoptosis in testicular germ cell tumor.2017
Author(s)
Yamada Y, Takayama KI, Fujimura T, Ashikari D, Obinata D, Takahashi S, Ikeda K, Kakutani S, Urano T, Fukuhara H, Homma Y, Inoue S.
-
Journal Title
Cancer Sci.
Volume: 108
Issue: 1
Pages: 32-41
DOI
Related Report
Peer Reviewed / Open Access
-
-
-
[Journal Article] Prognostic value of CD66b positive tumor-infiltrating neutrophils in testicular germ cell tumor.2016
Author(s)
Yamada Y, Nakagawa T, Sugihara T, Horiuchi T, Yoshizaki U, Fujimura T, Fukuhara H, Urano T, Takayama K, Inoue S, Kume H, Homma Y
-
Journal Title
BMC Cancer.
Volume: 16
Pages: 898-898
Related Report
Peer Reviewed
-
-
[Journal Article] Targeting Oct1 genomic function inhibits androgen receptor signaling and castration-resistant prostate cancer growth2016
Author(s)
Obinata D, Takayama K, Fujiwara K, Suzuki T, Tsutsumi S, Fukuda N, Nagase H, Fujimura T, Urano T, Homma Y, Aburatani H, Takahashi S and Inoue S.
-
Journal Title
Oncogene
Volume: ３５
Issue: 49
Pages: 6350-6358
DOI
Related Report
Peer Reviewed
-
-
-
[Journal Article] ABHD2, an androgen target gene, promotes prostate cancer cell proliferation and migration.2016
Author(s)
Obinata D, Takada S, Takayama K, Urano T, Ito A, Ashikari D, Fujiwara K, Yamada Y, Murata T, Kumagai J, Fujimura T, Ikeda K, Horie-Inoue K, Homma Y
-
Journal Title
Eur J Cancer 57
Volume: 57
Pages: 39-49
DOI
Related Report
Peer Reviewed
-
-
-
[Journal Article] Toremifene, a selective estrogen receptor modulator, significantly improved biochemical recurrence in bone metastatic prostate cancer: a randomized controlled phase II a trial.2015
Author(s)
Fujimura T, Takahashi S, Kume H, Urano T, Takayama K, Yamada Y, Suzuki M, Fukuhara H, Nakagawa T, Inoue S, Homma Y.
-
Journal Title
BMC Cancer.
Volume: 15
Issue: 1
Pages: 836-836
DOI
Related Report
Peer Reviewed / Open Access
-
-
-
-
-
-
-
-
-
-
-
[Presentation] [学術奨励賞（基礎部門）] Androgen-responsive long noncoding RNA CTBP1-AS promotes prostate cancer.2015
Author(s)
Takayama K, Horie-Inoue K, Katayama S, Suzuki T, Tsutsumi S, Ikeda K, Urano T, Fujimura T, Takagi K, Takahashi S, Homma Y, Ouchi Y, Aburatani H, Hayashizaki Y, Inoue S
Organizer
日本アンドロロジー学会第34回学術大会
Place of Presentation
福岡大学病院（福岡県・福岡市）
Year and Date
2015-06-26
Related Report
Invited
-
-
-
-
-
