The Department of Biochemistry and Molecular Biology at Colorado State University

Research excellence in the areas of Cellular Biochemistry, Structural Biology and Gene Expression

Jennifer K. Nyborg

Nyborg, Jennifer K. - Professor

Contact Information:

Jennifer.Nyborg@ColoState.edu

Office Number: 281 MRB

Phone Number: (970) 491-0420

Fax Number: (970) 491-0494

Research Title:

Transcriptional Deregulation in Leukemia Cells

Research Description:

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.

Selected Publications:

Selected publications since 1995

Geiger, T.R., Sharma, N., Kim, Y.-M., and Nyborg, J.K. The HTLV-1 Tax Protein Confers CBP/p300 Recruitment and Transcriptional Activation Properties to Phosphorylated CREB. Mol. Cell. Biol., in press (2007).

Ramírez, J.A. and Nyborg, J.K. Molecular Characterization of the HTLV-1 Tax Interaction with the KIX Domain of CBP/p300. J. Mol. Biol. 372, 958-969 (2007).

Lopez, D.I., Mick, J.E., and Nyborg, J.K. Purification of CREB to Apparent Homogeneity: Removal of Truncation Products and Contaminating Nucleic Acid. Protein Expression and Purification 55, 406-418 (2007).

Sharma, N., Lopez, D.I. and Nyborg, J.K. 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).

Kim, Y.-M., Ramírez, J.A., Mick, J.E., Giebler, H.A., Yan, J.-P. and Nyborg, J.K. 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).

Lemasson, I., Lewis, M., Hivin, P., Cavanagh, M-H., Polakowski, N., Thébault, S., Barbeau, B., Nyborg, J.K. and Mesnard, J.M. HTLV-1 bZIP protein interacts with the cellular transcription factor CREB to inhibit HTLV-1 transcription. J. Virology 81, 1543-1553 (2007).

Konesky, K.L., Nyborg, J.K. and Laybourn, P.J. Tax Abolishes Histone H1 Repression of p300 Acetyltransferase Activity at the HTLV-I Promoter. J. Virology, 80, 10542-10553 (2006).

Lemasson, I., Polakowski, N., Laybourn, P.J. and Nyborg, J.K. Tax-Dependent Displacement of Nucleosomes During transcriptional Activation of Human T-cell Leukemia Virus Type 1. J. Biol. Chem. 281,13075-13082 (2006).

Nyborg, J.K. and Peersen, O.B. That Zincing Feeling: The Effects of EDTA on the Behavior of Zinc-Binding Transcriptional Regulators. Biochem. J. 381, e3-e4 (2004).

Lemasson, I., Polakowski, N.J., Laybourn, P.J., and Nyborg, J.K. Transcription Regulatory Complexes Bind the Human T-cell Leukemia Virus 5 and 3 Long Terminal Repeats to Control Gene Expression. Mol. Cell. Biol. 24, 6117-6126 (2004).

Livengood, J.A. and Nyborg, J.K. The High Affinity Sp1 Binding Site in the HTLV-1 Promoter Contributes to Tax-Independent Basal Expression. Nuc. Acids Res. 32, 2829-2837 (2004).

Livengood, J.A., Fechter, E.J., Dervan, P.E., and Nyborg, J.K. Paradoxical Effects of DNA Binding Polyamides on HTLV-I Transcription. Frontiers in Bioscience 9, 3058-3067 (2004).

McBryant, S.J., Park, Y.-J., Abernathy, S.M., Laybourn, P.J., Nyborg, J.K. and Luger, K. Preferential binding of the histone (H3-H4)2 tetramer by NAP1 is mediated by the amino terminal histone tails. J. Biol. Chem. 278, 44574-44583 (2003).

Georges, S.A., Giebler, H.A., Cole, P.A., Luger, K., Laybourn, P.J., and Nyborg, J.K. Tax Recruitment of CBP/p300, via the KIX Domain, Reveals a Potent Requirement for Acetyltransferase Activity that is Chromatin-Dependent and Histone Tail-Independent. Mol. Cell. Biol. 23; 3392-3404 (2003).

Lemasson, I, Polakowski, N.J., Laybourn, P.J. and Nyborg, J.K. Transcription Factor Binding and Histone Modifications on the Integrated Proviral Promoter in HTLV-I-Infected T-Cells. J. Biol. Chem. 177; 49459-49465 (2002).

Livengood, J.A., Scoggin, K.E.S.,Van Orden, K., Edayathumangalam, R. McBryant, S.J., Laybourn, P.J. and Nyborg. J.K. p53 Interaction with the SRC-Interacting Domain of CBP/p300 Mediates Coactivator-Dependent Transcriptional Activity. J. Biol. Chem. 277; 9054-9061 (2002).

Georges, S. Kraus, W.L., Luger, K. Nyborg, J.K., Laybourn, P.J. p300-Mediated HTLV-I Tax Transactivation on Recombinant Chromatin Templates: Histone Tail Deletion Mimics Coactivator Function. Mol. Cell. Biol. 22; 127-137 (2002).

Scoggin, K. E. S., Ulloa, A. and Nyborg, J.K. The Oncoprotein Tax Binds the SRC-Interacting Domain of CBP/p300 to Mediate Transcriptional Activation. Mol. Cell. Biol. 16; 5520-5530 (2001).

Lemasson, I. and Nyborg, J.K. HTLV-I Tax Repression of p73beta is Mediated Through Competition for the C/H1 domain of CBP. J Biol Chem. 276;15720-15727 (2001).

Mick, J.E., Colgin, M.A., Brauweiler, A and Nyborg, J. K. Analysis of CREB mutants in Tax complex formation and transactivation. AIDS Research and Human Retroviruses, 16; 1597-1601 (2000).

Van Orden, K. and Nyborg, J.K. Insight into CBB function through the viral oncoprotein Tax. Gene Expression, in press (2000).

Giebler, H.A., Lemasson, I. and Nyborg, J.K. p53 recruitment of CBP mediated through phosphorylated CREB: A novel pathway for tumor suppressor regulation. Molec. Cell. Biol. 20:4849-4858 (2000).

Van Orden, K., Giebler, H.A., Lemasson, I., Gonzales, M. and Nyborg, J.K. Binding of p53 to the KIX domain of CBP: A potential link to HTLV-I associated leukemogenesis. J. Biol. Chem. 274, 26321-26328 (1999).

Lenzmeier, B.A., Baird, E.E., Dervan, P.B. and Nyborg, J.K. The Tax Protein-DNA Interaction is Essential for HTLV-I Transactivation in vitro. J. Mol. Biol. 291, 731-744 (1999).

Van Orden, K., Yan, J.-P. Ulloa, A. and Nyborg, J.K. 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).

Van Orden, K. and Nyborg, J.K. Binding of HTLV-I Tax to the Coactivator CBP Disrupts the Transcription Activity of c-Jun, in Molecular Pathogenesis of HTLV-I: a current perspective. eds. O. John Semmes and Marie-Louise Hammarskjold, ABI Professional Publications, (USA) (1999).

Lenzmeier, B.A. and Nyborg, J.K. Molecular Mechanisms of Viral Transcription and Cellular Deregulation Associated with the HTLV-I Tax Protein. Gene Ther. Mol. Biol. 3, 327-345 (1999).

Colgin, M.A. and Nyborg, J.K. The HTLV-I Oncoprotein Tax Inhibits the Transcriptional Activity of c-Myb through Competition for CBP. J. Virol. 72: 9396-9399 (1998).

Yan, J.-P., Garrus, J.E., Giebler, H.A., Stargell, L.A. and Nyborg, J.K. Molecular Interactions Between the Human T-Cell Leukemia Virus Tax Protein and the Cellular Coactivator CBP. J. Mol. Biol. 281: 395-400 (1998).

Brooks, P.A., Cockerell, G.L. and Nyborg. J.K. Activation of BLV Transcription by NF-kB and Tax. Virology 243:94-98 (1998).

Lenzmeier, B.A., Giebler, H.A. and Nyborg, J.K. HTLV-I Tax Requires Direct Access to DNA for Recruitment of CBP. Mol. Cell. Biol. 18:721-731 (1998).

Giebler, H.A., Loring, J., Van Orden, K., Colgin, M., Garrus, J., Escudero, K., Brauwieler, A. and Nyborg, J.K. Anchoring of CBP to the HTLV-I Promoter: A Molecular mechanism of Tax Transactivation. Mol. Cell. Biol. 17: 5156-5164 (1997).

Lenzmeier, B. and Nyborg, J.K. In vitro Transcription of Human T-cell Leukemia Virus Type I is RNA Polymerase II Dependent. J. Virology 71:2577-2580 (1997).

Brauweiler, A., Garrus, J.E., Reed, J.C. and Nyborg, J.K. Repression of Bax Gene Expression by the HTLV-I Tax Protein: Implications for Suppression of Apoptosis in Virally-Infected Cells. Virology 231: 135-140 (1997).

Gottesfeld, J.M., Johnson, D.L. and Nyborg, J.K. Transcriptional Activation of RNA Polymerase III-Dependent Genes by the HTLV-I Tax Protein. Mol Cell. Biol. 16: 1777-1785 (1996).

Uittenbogaard, M.N., Giebler, H.A., Reisman, D. and Nyborg, J.K. Transcriptional Repression of p53 by the Human T-Cell Leukemia Virus type I Tax Protein, J. Biol. Chem. 270: 28503-28506 (1995).

Brauweiler, A., Garl, P., Franklin, A.A., Giebler, H.A. and Nyborg, J.K. A Molecular Mechanism for HTLV-I Latency and Tax Transactivation. J. Biol. Chem. 270: 12814-12822 (1995).

Baranger, A.M., Palmer, C.R., Hamm, M.K., Giebler, H.A., Brauweiler, A., Nyborg, J.K. and Schepartz, A. Mechanism of DNA Binding Enhancement by the HTLV-I Transactivator Tax. Nature 376: 606-608 (1995).

NIH PubMed publications list for Jennifer K. Nyborg
(This is a link to an external site.)

Laboratory Web Page

http://www.nyborglab.com/

Mailing Address:

Dept of Biochemistry and Molecular Biology 1870

Colorado State University

Fort Collins, CO 80523-1870