Office: Mrb 275
Phone: (970) 491-0420
- Ph.D., University of California, Riverside
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.