2005 Fiscal Year Final Research Report Summary
The roles of Tax encoded by HTLV on cell proliferation
| Project/Area Number |
16390135
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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 |
Virology
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| Research Institution | KYOTO UNIVERSITY |
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Principal Investigator |
SHIMOTOHNO Kunitada Kyoto University, Institute for virus Research, Professor, ウイルス研究所, 教授 (10000259)
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| Project Period (FY) |
2004 – 2005
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| Keywords | HTLV / Tax / methylation / CREB / LTR / ATL / NFkB / transcription |
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| Research Abstract |
Human T-cell leukemia virus, HTLV, is a causative agent for the development of adult T-cell leukemia, ATL. Tax encoded by HTLV has been known to play important roles in the process of development of the tumor. However, precise mechanism of Tax in this process still remains to be elucidated. Here, we focused to clarify the roles of Tax in regulations of cell proliferation, transcriptional regulation and epigenetic regulation, and found the following evidence ; (1)Upon Tax expression, a cellular protein, p21waf, which involves in cell cycle regulation, was up-regulated. We analyzed the role of p21waf in Tax expressing cells using Rat1 cell in which endogenous p21waf expression is impaired because of methylation of its promoter. By comparison of cells expressing ectopic Tax, and those expressing tax plus p21waf, we observed that the cells expressing Tax plus p21waf showed characteristics nature, resistant to apoptosis. (2)By analyzing molecular mechanism of gaining anti-apoptotic function
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in those cells expressing Tax and p21waf, we found that these cells activated NFkB signaling. In particular, it is note worthy that activation of NFkB signaling was through a non-conventional pathway. Thus, we believe that p21waf contributes to activate this signaling together with Tax. (3)Expression of HTLV is often silenced by methylation of its LTR. Host cells may have developed the mechanism to shut down proliferation of HTLV by this way. However, by stimulation of proliferation of the infected cells, re-activation of gene expression of HTLV often occurs. We analyzed whether or not Tax activate transcription from methylated LTR. This analysis was conducted under comparison with transacting activity of Tax for various methylated promoter. We found that the promoter containing CRE sequence could be activated by Tax irrespective to presence of CREB, which suggests not only the methylated LTR but also other cellular promoters with CRE can be the target for Tax even heavily methylated. Thus, this study provides a new clue to understand more complicated mechanism of Tax in regard to transcriptional regulation. Less
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Research Products
(7 results)
