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Kaposi Sarcoma Herpesvirus: New Perspectives pp 101–136Cite as

Structure and Function of Latency-Associated Nuclear Antigen

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Part of the book series: Current Topics in Microbiology and Immunology ((CT MICROBIOLOGY,volume 312))

Abstract

Latency-associated nuclear antigen (LANA) encoded by open reading frame 73 (ORF73) is the major latent protein expressed in all forms of KSHV-associated malignancies. LANA is a large (222–234 kDa) nuclear protein that interacts with various cellular as well as viral proteins. LANA has been classified as an oncogenic protein as it dysregulates various cellular pathways including tumor suppressor pathways associated with pRb and p53 and can transform primary rat embryo fibroblasts in cooperation with the cellular oncogene Hras. It associates with GSK-3β, an important modulator of Wnt signaling pathway leading to the accumulation of cytoplasmic β-catenin, which upregulates Tcf/Lef regulated genes after entering into the nucleus. LANA also blocks the expression of RTA, the reactivation transcriptional activator, which is critical for the latency to lytic switch, and thus helps in maintaining viral latency. LANA tethers the viral episomal DNA to the host chromosomes by directly binding to its cognate binding sequence within the TR region of the genome through its C terminus and to the nucleosomes through the N terminus of the molecule. Tethering to the host chromosomes helps in efficient partitioning of the viral episomes in the dividing cells. Disruptions of LANA expression led to reduction in the episomal copies of the viral DNA, supporting its role in persistence of the viral DNA. The functions known so far suggest that LANA is a key player in KSHV-mediated pathogenesis.

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  1. Department of Microbiology and Tumor Virology Program of the Abramson Comprehensive Cancer Center, University of Pennsylvania School of Medicine, 201E Johnson Pavilion, 3610 Hamilton Walk, Philadelphia, PA, 19104, USA

    S. C. Verma, K. Lan & E. Robertson

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  1. S. C. Verma
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  2. K. Lan
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  1. Wolfson Institute for Biomedical Research, University College London, Gower Street, London, WC1E 6BT, UK

    Chris Boshoff MRCP, Ph.D.

  2. Wohl Virion Centre, Division of Infection and Immunity, University College London, 46 Cleveland Street, London, W1T 4JF, UK

    Robin A. Weiss Ph.D.

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Verma, S.C., Lan, K., Robertson, E. (2007). Structure and Function of Latency-Associated Nuclear Antigen. In: Boshoff, C., Weiss, R.A. (eds) Kaposi Sarcoma Herpesvirus: New Perspectives. Current Topics in Microbiology and Immunology, vol 312. Springer, Berlin, Heidelberg . https://doi.org/10.1007/978-3-540-34344-8_4

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