Analysis of ATL leukemogenesis through breakage of defense mechanism of HTLV-1 infection
Project/Area Number |
25293081
|
Research Category |
Grant-in-Aid for Scientific Research (B)
|
Allocation Type | Partial Multi-year Fund |
Section | 一般 |
Research Field |
Pathological medical chemistry
|
Research Institution | University of Miyazaki |
Principal Investigator |
|
Co-Investigator(Kenkyū-buntansha) |
TANIWAKI Masfumi 京都府立医科大学, 医学研究科, 教授 (80163640)
NAKAHATA Shingo 宮崎大学, 医学部, 助教 (80437938)
ICHIKAWA Tomonaga 宮崎大学, 医学部, 助教 (80586230)
KANEDA Kazuko 宮崎大学, 医学部, 助教 (00533209)
NISHIKATA Ichiro 宮崎大学, 医学部, 助教 (50253844)
|
Project Period (FY) |
2013-04-01 – 2016-03-31
|
Project Status |
Completed (Fiscal Year 2015)
|
Budget Amount *help |
¥17,420,000 (Direct Cost: ¥13,400,000、Indirect Cost: ¥4,020,000)
Fiscal Year 2015: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2014: ¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000)
Fiscal Year 2013: ¥8,320,000 (Direct Cost: ¥6,400,000、Indirect Cost: ¥1,920,000)
|
Keywords | HTLV-1 / 成人T細胞白血病 / NDRG2 / PTEN / NF-kB / NIK / ATLL / 感染防御 / リン酸化異常 / ゲノム異常 |
Outline of Final Research Achievements |
Constitutive PI3K/AKT activation has a causal role in adult T-cell leukaemia-lymphoma (ATLL) and other cancers. ATLL cells do not harbour genetic alterations in PTEN and PI3KCA but express high levels of PTEN that is highly phosphorylated at its C-terminal tail. Here we report a mechanism for the N-myc downstream-regulated gene 2 (NDRG2)-dependent regulation of PTEN phosphatase activity via the dephosphorylation of PTEN at the Ser380, Thr382 and Thr383 cluster within the C-terminal tail. We show that NDRG2 is a PTEN-binding protein that recruits protein phosphatase 2A (PP2A) to PTEN. The expression of NDRG2 is frequently downregulated in ATLL, resulting in enhanced phosphorylation of PTEN at the Ser380/Thr382/Thr383 cluster and enhanced activation of the PI3K-AKT pathway. Given the high incidence of T-cell lymphoma and other cancers in NDRG2-deficient mice, PI3K-AKT activation via enhanced PTEN phosphorylation may be critical for the development of cancer.
|
Report
(4 results)
Research Products
(54 results)
-
-
-
[Journal Article] Superoxide-Generating Nox5α Is Functionally Required for the Human T-Cell Leukemia Virus Type 1-Induced Cell Transformation Phenotype.2015
Author(s)
Shigemura T, Shiohara M, Kato M, Furuta S, Kaneda K, Morishita K, Hasegawa H, Fujii M, Gorlach A, Koike K, Kamata T.
-
Journal Title
J Virol.
Volume: 89
Issue: 17
Pages: 9080-9
DOI
Related Report
Peer Reviewed / Open Access
-
[Journal Article] Furin-dependent CCL17-fused recombinant toxin controls HTLV-1 infection by targeting and eliminating infected CCR4-expressing cells in vitro and in vivo.2015
Author(s)
Okuma K, Hiyoshi M, Tateyama S, Takizawa K, Saito M, Kuramitsu M, Araki K, Morishita K, Okada S, Yamamoto N, Biragyn A, Yamaguchi K, Hamaguchi I.
-
Journal Title
Retrovirology
Volume: 12
Issue: 1
Pages: 1-14
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
-
-
-
-
-
[Journal Article] Increased plasma lactoferrin levels in leucocytapheresis therapy in patients with rheumatoid arthritis.2014
Author(s)
Miyauchi S, Umekita K, Hidaka T, Umeki K, Aratake Y, Takahashi N, Sawaguchi A, Nakatake A, Morinaga I, Morishita K, Okayama A.
-
Journal Title
Rheumatology (Oxford).
Volume: 53
Issue: 11
Pages: 1966-72
DOI
Related Report
Peer Reviewed
-
[Journal Article] Development of a complete human anti-human transferrin receptor C antibody as a novel marker of oral dysplasia and oral cancer.2014
Author(s)
5.Nagai K, Nakahata S, Shimosaki S, Tamura T, Kondo Y, Baba T, Taki T, Taniwaki M, Kurosawa G, Sudo Y, Okada S, Sakoda S, Morishita K
-
Journal Title
Cancer Med.
Volume: 3
Issue: 4
Pages: 18-26
DOI
Related Report
Peer Reviewed
-
[Journal Article] Identification of a bioactive compound against adult T-cell leukemia from bitter gourd Seed2014
Author(s)
) Kai H, Akamatsu E, Torii E, Ko-dama H, Yukizaki C, Akagi I, Ino H, Sakakibara Y, Suiko M, Yamamoto I, Okayama A, Mor-ishita K, Kataoka H, Matsuno K
-
Journal Title
Plants
Volume: 3
Issue: 1
Pages: 18-26
DOI
Related Report
Peer Reviewed
-
[Journal Article] Loss of NDRG2 expression activates PI3K-AKT signalling via PTEN phosphorylation in ATLL and other cancers.2014
Author(s)
Nakahata S, Ichikawa T, Maneesaay P, Saito Y, Nagai K, Tamura T, Manachai N, Yamakawa N, Hamasaki M, Kitabayashi I, Arai Y, Kanai Y, Taki T, Abe T, Kiyonari H, Shimoda K, Ohshima K, Horii A, Shima H, Taniwaki M, Yamaguchi R, Morishita K.
-
Journal Title
Nat Commun
Volume: in press
Issue: 1
Pages: 3393-3393
DOI
Related Report
Peer Reviewed / Open Access
-
-
-
-
-
[Journal Article] Maintenance of the hematopoietic stem cell pool in bone marrow niches by EVI1-regulated GPR562013
Author(s)
Saito Y., Kaneda K., Suekane A., Ichihara E., Nakahata S., Yamakawa N., Nagai K., Mizuno N., Kogawa K., Miura I., Itoh H., and Morishita K..
-
Journal Title
Leukemia
Volume: 27
Issue: 8
Pages: 1637-1649
DOI
Related Report
Peer Reviewed
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-