期刊
JOURNAL OF VIROLOGY
卷 82, 期 1, 页码 49-59出版社
AMER SOC MICROBIOLOGY
DOI: 10.1128/JVI.01497-07
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- Intramural NIH HHS Funding Source: Medline
- NATIONAL CANCER INSTITUTE [Z01BC005254, ZIABC005691, Z01BC005691, ZIABC005254] Funding Source: NIH RePORTER
Human T-lymphotropic virus type 1 (HTLV-1) is the etiologic agent for adult T-cell leukemia. The HTLV-1-encoded protein Tax transactivates the viral long terminal repeat and plays a critical role in virus replication and transformation. Previous work from our laboratory demonstrated that coactivator-associated arginine methytransferase 1, a protein arginine methytransferase, was important for Tax-mediated transactivation. To further investigate the role of methyltransferases in viral transcription, we utilized adenosine-2,3-dialdehyde (AdOx), an adenosine analog and S-adenosylmethionine-dependent methyltransferase inhibitor. The addition of AdOx decreased Tax transactivation in C81, Hut102, and MT-2 cells. Unexpectedly, we found that AdOx potently inhibited the growth of HTLV-1-transformed cells. Further investigation revealed that AdOx inhibited the Tax-activated NF-kappa B pathway, resulting in reactivation of p53 and induction of p53 target genes. Analysis of the NF-kappa B pathway demonstrated that AdOx treatment resulted in degradation of the I kappa B kinase complex and inhibition of NF-kappa B through stabilization of the NF-kappa B inhibitor I kappa B alpha. Our data further demonstrated that AdOx induced G(2)/M cell cycle arrest and cell death in HTLV-1-transformed but not control lymphocytes. These studies demonstrate that protein methylation plays an important role in NF-kappa B activation and survival of HTLV-1-transformed cells.
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