2012 Fiscal Year Final Research Report
Investigation of the molecular mechanisms of constitutive NF-kBactivation for the identification of therapeutic targets of adult T-cell leukemia cells
| Project/Area Number |
22790905
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| Research Category |
Grant-in-Aid for Young Scientists (B)
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| Allocation Type | Single-year Grants |
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| Research Field |
Hematology
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| Research Institution | Tokyo Medical and Dental University |
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Principal Investigator |
SAITOH Yasunori 東京医科歯科大学, 医歯学総合研究科・ウイルス制御学, 助教 (00516312)
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| Project Period (FY) |
2010 – 2012
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| Keywords | 血液腫瘍学 |
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| Research Abstract |
Adult T-cell leukemia (ATL) is a T-cell neoplasm caused by Human T-cell leukemia virus type I infection. Previous reports described that the ubiquitin-editing enzyme A20 protects cytokine- or NK-induced cell death of endothelial cells via inhibiting caspase-8 activation. I found that the A20 protein and mRNA expressions were detectable in ATL cells in contrast to some of B-cell lymphoma cell lines with a somatic mutation and/or deletion of A20. Interestingly, quantitative RT-PCR analysis revealed that the A20 mRNA expression was frequently up-regulated in PBMCs derived from ATL patients. And A20 was found to be required for the growth of ATL-derived and HTLV-I-transformed cells. RNA-interference mediated knock-down of A20 induced the activation of apoptosis initiator caspase-8 concomitant with the activation of downstream effector caspase-3/7. In addition, I found that A20 physically interacts with caspase-8. Importantly, depletion of A20 suppressed the growth of ATL cells and increased the annexin V-positive population. These results suggest that A20 contributes to the survival of ATL cells and implicates A20 as a therapeutic molecular target for ATL therapy.
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[Journal Article] Neutrophil extracellular traps mediate a host defense response to human immunodeficiency virus-12012
Author(s)
Saitoh T, Komano J, Saitoh Y, Misawa T, Takahama M, Kozaki T, Uehata T, Iwasaki H, Omori H, Yamaoka S, Yamamoto N, Akira S
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Journal Title
Cell HostMicrobe
Volume: 12
Pages: 109-116
Peer Reviewed
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