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NF-kappa B activation of the cytomegalovirus enhancer is mediated by a viral transactivator and by T cell stimulation.
EMBO J. 1989 Dec 20; 8(13):4251-8.EJ

Abstract

The expression of cytomegalovirus alpha (immediate early) genes is under control of an enhancer that carries signals for strong constitutive expression as well as response elements for transactivation by viral proteins. We have used synthetic oligonucleotides representing the 16, 18 and 19 bp repeat elements within the enhancer to investigate the role of virus-induced cellular transcription factors in enhancer activation. We show that the transcription factor NF-kappa B, which binds to the 18 bp repeat, plays a central role in enhancer activation in infected human fibroblasts and that activation is mediated by the product of the viral gene ie1. The simian immunodeficiency virus kappa B site can functionally substitute for the 18 bp element in transient transactivation assays and can also compete efficiently for specific binding to the 18 bp repeat element in vitro. Point mutations in the NF-kappa B site within the 18 bp element disrupt ie1-mediated transactivation and binding. We have found that the characteristics of the 18 bp binding factor from human fibroblasts are indistinguishable from NF-kappa B induced by phorbol ester plus mitogen treatment of T lymphocytes, as determined by gel mobility shift assay as well as protection of the binding site from chemical cleavage. Furthermore, T cell stimulation mediates activation of the viral enhancer via kappa B sites, an observation that may be important in the interaction of cytomegalovirus with the naturally infected human host. Thus, NF-kappa B plays a central role as a target for enhancer activation via viral and cellular factors.

Authors+Show Affiliations

Department of Microbiology and Immunology, Stanford University School of Medicine, CA 94305.No affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, P.H.S.

Language

eng

PubMed ID

2556267

Citation

Sambucetti, L C., et al. "NF-kappa B Activation of the Cytomegalovirus Enhancer Is Mediated By a Viral Transactivator and By T Cell Stimulation." The EMBO Journal, vol. 8, no. 13, 1989, pp. 4251-8.
Sambucetti LC, Cherrington JM, Wilkinson GW, et al. NF-kappa B activation of the cytomegalovirus enhancer is mediated by a viral transactivator and by T cell stimulation. EMBO J. 1989;8(13):4251-8.
Sambucetti, L. C., Cherrington, J. M., Wilkinson, G. W., & Mocarski, E. S. (1989). NF-kappa B activation of the cytomegalovirus enhancer is mediated by a viral transactivator and by T cell stimulation. The EMBO Journal, 8(13), 4251-8.
Sambucetti LC, et al. NF-kappa B Activation of the Cytomegalovirus Enhancer Is Mediated By a Viral Transactivator and By T Cell Stimulation. EMBO J. 1989 Dec 20;8(13):4251-8. PubMed PMID: 2556267.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - NF-kappa B activation of the cytomegalovirus enhancer is mediated by a viral transactivator and by T cell stimulation. AU - Sambucetti,L C, AU - Cherrington,J M, AU - Wilkinson,G W, AU - Mocarski,E S, PY - 1989/12/20/pubmed PY - 1989/12/20/medline PY - 1989/12/20/entrez SP - 4251 EP - 8 JF - The EMBO journal JO - EMBO J VL - 8 IS - 13 N2 - The expression of cytomegalovirus alpha (immediate early) genes is under control of an enhancer that carries signals for strong constitutive expression as well as response elements for transactivation by viral proteins. We have used synthetic oligonucleotides representing the 16, 18 and 19 bp repeat elements within the enhancer to investigate the role of virus-induced cellular transcription factors in enhancer activation. We show that the transcription factor NF-kappa B, which binds to the 18 bp repeat, plays a central role in enhancer activation in infected human fibroblasts and that activation is mediated by the product of the viral gene ie1. The simian immunodeficiency virus kappa B site can functionally substitute for the 18 bp element in transient transactivation assays and can also compete efficiently for specific binding to the 18 bp repeat element in vitro. Point mutations in the NF-kappa B site within the 18 bp element disrupt ie1-mediated transactivation and binding. We have found that the characteristics of the 18 bp binding factor from human fibroblasts are indistinguishable from NF-kappa B induced by phorbol ester plus mitogen treatment of T lymphocytes, as determined by gel mobility shift assay as well as protection of the binding site from chemical cleavage. Furthermore, T cell stimulation mediates activation of the viral enhancer via kappa B sites, an observation that may be important in the interaction of cytomegalovirus with the naturally infected human host. Thus, NF-kappa B plays a central role as a target for enhancer activation via viral and cellular factors. SN - 0261-4189 UR - https://www.unboundmedicine.com/medline/citation/2556267/NF_kappa_B_activation_of_the_cytomegalovirus_enhancer_is_mediated_by_a_viral_transactivator_and_by_T_cell_stimulation_ L2 - https://onlinelibrary.wiley.com/resolve/openurl?genre=article&sid=nlm:pubmed&issn=0261-4189&date=1989&volume=8&issue=13&spage=4251 DB - PRIME DP - Unbound Medicine ER -