2005 Fiscal Year Final Research Report Summary
Analysis of expression control of the Bim gene.
| Project/Area Number |
16390279
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Hematology
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| Research Institution | HIROSHIMA UNIVERSITY |
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Principal Investigator |
INABA Toshiya Hiroshima University, Research Institute for Radiation Biology and Medicine, Professor, 原爆放射線医科学研究所, 教授 (60281292)
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| Project Period (FY) |
2004 – 2005
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| Keywords | mRNA stability / cytokine / heat shock protein / co-chaperone / Bim / p27 / Hsc70 |
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| Research Abstract |
Previous gene-targeting studies indicated that Bim, a BH3-only death activator, and p27^<KIP1>, a cyclin-dependent kinase inhibitor, regulate total cell number in the body. Cytokines contribute to this process primarily by negatively regulating the steady-state levels of Bim and p27 mRNAs. We discovered a novel mechanism for cytokine-mediated post-transcriptional regulation of Bim and p27 mRNA levels via the activity of Heat shock cognate protein 70 (Hsc70), which enhances the stability of specific mRNAs by binding to AU-rich elements (AREs) in their 3'-untranslated regions. The RNA-binding potential of Hsc70 is regulated by co-chaperones, including Bag-4 (also SODD), CHIP, Hip and Hsp40. Cytokines that down-regulate Bim and p27 operate via Ras-activated signaling pathways, which in turn control the expression or function of these co-chaperones. Thus, exposure of cells to cytokines ultimately leads to the destabilization of Bim and p27 mRNAs and the promotion of cell division and survival. This unanticipated role for a chaperone/co-chaperone complex in the control of mRNA stability appears to be critical for hematopoiesis and leukemogenesis.
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[Journal Article] Regulation of annexin II by cytokine-initiated signaling pathways and E2A-HLF oncoprotein.2004
Author(s)
Matsunaga T., Inaba T., Matsui H., Okuya M., Kinoshita T., Miyajima A., Funabiki T., Endo M., Inukai T., Look AT., Kurosawa H.
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Journal Title
Blood 103
Pages: 3185-3191
Description
「研究成果報告書概要(欧文)」より
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