Nicholas Polakowski

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BACKGROUND Human T-cell leukemia virus type 1 (HTLV-1) is the etiologic agent of adult T-cell leukemia, a malignancy characterized by uncontrolled proliferation of virally-infected CD4+ T-cells. Hypercalcemia and bone lesions due to osteoclast-mediated bone resorption are frequently associated with more aggressive forms of the disease. The HTLV-1 provirus(More)
The homologous cellular coactivators p300 and CBP contain intrinsic lysine acetyl transferase (termed HAT) activity. This activity is responsible for acetylation of several sites on the histones as well as modification of transcription factors. In a previous study, we found that HBZ, encoded by the Human T-cell Leukemia Virus type 1 (HTLV-1), binds to(More)
TFIIIA is required to activate RNA polymerase III transcription from 5S RNA genes. Although all known TFIIIA homologs harbor nine zinc fingers that mediate DNA binding, very limited sequence homology is found among these proteins, which reflects unique properties of some TFIIIA homologs. For example, the Acanthamoeba castellanii homolog directly regulates(More)
Adult T-cell leukemia (ATL) is one of the primary diseases caused by Human T-cell Leukemia Virus type 1 (HTLV-1) infection. The virally-encoded Tax protein is believed to initiate early events in the development of this disease, as it is able to promote immortalization of T-cells and transformation of other cell types. These processes may be aided by the(More)
Adult T-cell leukemia (ATL) is an often fatal malignancy caused by infection with the complex retrovirus, human T-cell Leukemia Virus, type 1 (HTLV-1). In ATL patient samples, the tumor suppressor, p53, is infrequently mutated; however, it has been shown to be inactivated by the viral protein, Tax. Here, we show that another HTLV-1 protein, HBZ, represses(More)
Brain-Derived Neurotrophic Factor (BDNF) is a neuro-trophin that generally promotes neuronal proliferation, survival and plasticity. These effects occur through cellular secretion and subsequent binding of BDNF to its cognate receptor, TrkB, which promotes paracrine and autocrine signaling cascades. A BDNF/TrkB autocrine loop has been implicated in the(More)
HBZ is one of the HTLV-1-encoded proteins known to affect transcription. We previously found that this viral protein interacts with the homologous cellular coacti-vators p300 and CBP. These large coactivators play an integral role in regulating expression of numerous genes, as they are known to bind more than 400 proteins that function to regulate(More)
The viral protein Tax utilizes interactions with many tran-scriptional regulatory proteins to modulate cellular gene expression and to activate transcription of the Human T-cell Leukemia Virus type 1(HTLV-1) provirus. In some cases it is possible that effects of Tax on cellular genes involve direct association of the viral protein with the promoter of the(More)
We previously reported that HTLV-1 basic leucine zipper factor (HBZ) interacts with the cellular coactivator p300 in cells derived from ATL patients. We further determined that HBZ directly binds to the histone acetyltrans-ferase (HAT) domain of both p300 and its homologue CBP. HAT activity transfers an acetyl group to lysine residues on histone tails and(More)
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