Pim-1 kinase activates Cdc25A phosphatase, the transcriptional target of c-Myc
Project/Area Number |
11671354
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Research Category |
Grant-in-Aid for Scientific Research (C)
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Allocation Type | Single-year Grants |
Section | 一般 |
Research Field |
Cerebral neurosurgery
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Research Institution | The University of Tokyo |
Principal Investigator |
MOCHIZUKI Toshihiro The University Hospital, Neurosurgery, Staff, 医学部・付属病院, 助手 (30302706)
|
Co-Investigator(Kenkyū-buntansha) |
ASAI Akio The University Hospital, Neurosurgery, Assistant Professor, 医学部・付属病院, 講師 (50231858)
植木 敬介 東京大学, 医学部・付属病院, 助手 (20302705)
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Project Period (FY) |
1999 – 2000
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Project Status |
Completed (Fiscal Year 2000)
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Budget Amount *help |
¥3,400,000 (Direct Cost: ¥3,400,000)
Fiscal Year 2000: ¥1,400,000 (Direct Cost: ¥1,400,000)
Fiscal Year 1999: ¥2,000,000 (Direct Cost: ¥2,000,000)
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Keywords | pim-1 / c-myc / cdc25A / apoptosis / アポートシス / 遺伝子治療 |
Research Abstract |
The pim-1 oncogene encodes a serine/threonine kinase (Pim-1) involved in the transduction of cytokine-triggered mitogenic signals. Pim-1 is unique in that it closely cooperates with c-Myc not only in oncogenesis but also in apoptosis induction. However, the molecular basis of Pim-1 function remains poorly understood, largely because the downstream effector molecule (s) for Pim-1 kinase has not been identified. Here we provide several lines of evidence that Cdc25A cell cycle phosphatase, a direct transcriptional target for c-Myc, is a substrate for Pim-1 kinase and functions as an effector for Pim-1. We found that Pim-1 physically interacts with Cdc25A both in vitro and in vivo and phosphorylates Cdc25A.We also observed that Pim-1-mediated phosphorylation of Cdc25A increases its phosphatase activity. In addition, wild-type Pim-1, but not kinase-inactive Pim-1, enhanced Cdc25A-mediated cellular transformation and apoptosis. Our results indicate that Cdc25A might be a key molecule that links Pim-1 and c-Myc and also ties Pim-1-mediated mitogenic signals to cell cycle machinery.
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Report
(3 results)
Research Products
(10 results)
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[Publications] Chi S,Kitanaka C,Noguchi K,Mochizuki,T,Nagashima Y,Shirouzu M,Fujita H,Yoshida M,Chen W,Asai A,Himeno M,Yokoyama S,Kuchino Y.: "Oncogenic Ras triggers cell suicide through the activation of a caspase-independent cell death program in human cancer cells."Oncogene. 18(13). 2281-2290 (1999)
Description
「研究成果報告書概要(和文)」より
Related Report
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[Publications] Chi S, Kitanaka C, Noguchi K, Mochizuki T, Nagashima Y, Shirouzu M, Fujita H, Yoshida M, Chen W, Asai A, Himeno M, Yokoyama S, Kuchino Y: "Oncogenic Ras triggers cell suicide through the activation of a caspase-independent cell death program in human cancer cells"Oncogene.. 18(13). 2281-90 (1999)
Description
「研究成果報告書概要(欧文)」より
Related Report
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