This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowReprints and Permissions
Right arrow Copyright Information
Right arrow Books from ASM Press
Right arrow MicrobeWorld
Citing Articles
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Dasgupta, A.
Right arrow Articles by Brady, J. N.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Dasgupta, A.
Right arrow Articles by Brady, J. N.

 Previous Article  |  Next Article 

Journal of Virology, January 2008, p. 49-59, Vol. 82, No. 1
0022-538X/08/$08.00+0     doi:10.1128/JVI.01497-07
Copyright © 2008, American Society for Microbiology. All Rights Reserved.

Inhibition of Methyltransferases Results in Induction of G2/M Checkpoint and Programmed Cell Death in Human T-Lymphotropic Virus Type 1-Transformed Cells{triangledown}

Arindam Dasgupta, Kyung-Jin Jung, Soo-Jin Jeong, and John N. Brady*

Virus Tumor Biology Section, Laboratory of Cellular Oncology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, 41 Medlars Dr., Building 41, Room B201, Bethesda, Maryland 20892

Received 9 July 2007/ Accepted 5 October 2007

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 G2/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.

* Corresponding author. Mailing address: Virus Tumor Biology Section, Laboratory of Cellular Oncology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, 41 Medlars Dr., Building 41, Room B201, Bethesda, MD 20892. Phone: (301) 496-0986. Fax: (301) 496-4951. E-mail: bradyj{at}mail.nih.gov

{triangledown} Published ahead of print on 17 October 2007.

Journal of Virology, January 2008, p. 49-59, Vol. 82, No. 1
0022-538X/08/$08.00+0     doi:10.1128/JVI.01497-07
Copyright © 2008, American Society for Microbiology. All Rights Reserved.





Copyright © 2009 by the American Society for Microbiology.   For an alternate route to Journals.ASM.org, visit: http://intl-journals.asm.org | More Info»