Abstract
The HTLV-I oncoprotein Tax is required for high level viral transcription and is strongly linked to HTLV-I - associated malignant transformation. Tax stimulates HTLV-I transcription through high affinity binding to the KIX domain of CBP, a pleiotropic coactivator. Several cellular proteins, including c-jun, also bind to KIX and utilize CBP as a coactivator. To test whether Tax binding to KIX may disable cellular CBP function, we examined the potential interplay between Tax and c-jun for binding to KIX. We show that Tax represses the transcription function of c-jun in vivo and demonstrate that both transcription factors bind to an overlapping minimal region of KIX in vitro. c-jun binding to KIX is displaced by Tax, indicating that their binding is mutually exclusive and providing a molecular basis for the observed repression. The competition between Tax and cellular transcription factors for CBP represents a novel pathway for HTLV-I dependent deregulation of gene expression, and may have significant implications for cellular homeostasis and transformation in the HTLV-I infected T-cell.
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Acknowledgements
We thank Katie Campbell, Kevin Lumb and James Bamburg for gifts of proteins, and Robert Harrod and Chou-Zen Giam for the Tax mutant plasmids. We also thank Brian Lenzmeier and Holli Giebler for critical reading and discussions of the manuscript. This work was supported by a grant from the American Cancer Society (VM-170).
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Van Orden, K., Yan, Jp., Ulloa, A. et al. Binding of the human T-cell leukemia virus Tax protein to the coactivator CBP interferes with CBP-mediated transcriptional control. Oncogene 18, 3766–3772 (1999). https://doi.org/10.1038/sj.onc.1202703
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DOI: https://doi.org/10.1038/sj.onc.1202703
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