Office: MRB 275
Phone: (970) 491-0420
Website: http://www.nyborglab.com
Education
- Ph.D., University of California, Riverside
About
The human T-cell leukemia virus (HTLV-I) is associated with a variety of clinical disorders, including an aggressive and fatal malignancy called adult T-cell leukemia (ATL). It is estimated that between 11 and 20 million people worldwide are infected with HTLV-I, and while most infected individuals remain asymptomatic, a small percentage develop ATL. A single HTLV-I-encoded protein, called Tax, has been strongly implicated in the etiology of the disease. Tax is critical to the viral life cycle, as it activates HTLV-I transcription. Recent studies demonstrate that the cellular coactivator CBP/p300 associates with Tax to potentiate transcriptional activation of the viral genome. CBP/p300 is a coactivator that regulates transcription through interaction with a wide variety of structurally unrelated transcription factors. CBP/p300 belongs to a novel class of recently described transcriptional coactivators proteins that possess histone acetyltransferase (HAT) activity, and appear to play a role in gene-specific activation through modulation of chromatin structure. Although the precise role of the HAT activity of CBP/p300 is unknown, there is a strong link between abnormalities in acetylase function, aberrant chromatin acetylation, and human cancers. These observations suggest that alterations in expression of CBP/p300 expression and/or function is a common denominator in many human malignancies, especially leukemias. The strong correlation between CBP/p300 deregulation and human malignancies forms the basis for the premise that the physical interaction between CBP/p300 and Tax plays a causal role in neoplastic transformation of the HTLV-I infected T-cell. My laboratory is exploring CBP/p300 transcription function using both in vitro and in vivo approaches. Our methods should allow biochemical dissection of the Tax-CBP/p300 interactions that accompany transcriptional activation. The outcome of our research may reveal basic aspects of CBP/p300 and Tax function as they pertain to gene regulation, chromatin structure, and leukemogenesis.
Publications
- The Coactivators CBP/p300 and the Histone Chaperone NAP-1 Promote Transcription-Independent Nucleosome Eviction at the HTLV-1 Promoter.Proc. Natl. Acad. Sci. USA 105, 7959-7963, 2008
- he HTLV-1 Tax Protein Confers CBP/p300 Recruitment and Transcriptional Activation Properties to Phosphorylated CREB.Mol. Cell. Biol. 28, 1383-1392 , 2008
- Tax and the Proto-Oncogene Bcl-3 Form a Complex that Represses HTLV-I Transcription via Displacement of p300.J Virol. 82, 11939-11947, 2008
- RGS13 acts as a nuclear repressor of CREB.Molecular Cell, 31, 660-670, 2008
- Molecular Characterization of the HTLV-1 Tax Interaction with the KIX Domain of CBP/p300.J. Mol. Biol. 372, 958-969 , 2007
- Purification of CREB to Apparent Homogeneity: Removal of Truncation Products and Contaminating Nucleic Acid.Protein Expression and Purification 55, 406-418, 2007
- DNA Binding and Phosphorylation Induce Conformational Alterations in the Kinase Inducible Domain of CREB: Implications for the Mechanism of CREB Transcription Function.J. Biol. Chem. 282, 19872-19883, 2007
- Molecular Characterization of the Tax-containing HTLV-1 Enhancer Complex Reveals a Prominent Role for CREB Phosphorylation in Tax Transactivation.J. Biol. Chem. 282, 18750-18757, 2007
- HTLV-1 bZIP protein interacts with the cellular transcription factor CREB to inhibit HTLV-1 transcription.J. Virology 81, 1543-1553 , 2007
- Tax Abolishes Histone H1 Repression of p300 Acetyltransferase Activity at the HTLV-I Promoter. J. Virology, 80, 10542-10553, 2006
