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出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2012/04/16 12:50:42」(JST)

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The latency-associated nuclear antigen or LANA-1, is a Kaposi's sarcoma-associated herpesvirus (KSHV) latent protein which has been suspected of playing a crucial role in modulating viral and cellular gene expression.^[1]^[2]^[3]. LANA was found by Moore and colleagues as a speckled nuclear antigen present in primary effusion lymphoma cells that reacts with antibodies from patients with KS.^[4] It is commonly used as an antigen in blood tests to detect antibodies in persons that have been exposed to KSHV.

KSHV or Human herpesvirus 8 (HHV-8) has been identified as the etiological agent of Kaposi’s sarcoma (KS) and certain AIDS-associated lymphomas. As KSHV establishes latent infection in tumorous foci^{[disambiguation needed ]}, it invariably expresses high levels of the viral LANA protein, which is necessary and sufficient to maintain the KSHV episome.

Encoded by ORF73, LANA-1 is one of few HHV-8 encoded proteins that is highly expressed in all latently infected tumour cells; specifically, it is a 222–234 kDa phosphoprotein with an acidic internal repeat domain flanked by a carboxy-terminal domain and an amino-terminal domain.^[3] LANA-1 acts as a transcriptional regulator, and it has been implicated directly in oncogenesis because of its ability to bind to the tumour-suppressing protein p53 and to the retinoblastoma protein pRb. This leads to the inactivation of p53-dependent promoters and induction of E2F-dependent genes.^[5]^[6]

Studies have also shown that LANA-1 can transactivate the promoter of the reverse transcriptase subunit of the human telomerase holoenzyme,^[6] thus overextending a critical step in cellular transformation.^[7] Paradoxically, LANA-1 has been shown to be involved in transcriptional repression ^[8]^[9]^[10] and can, moreover, interact with the mSin3/HDAC1 co-repressor complex.^[9]

It has been also shown to interact with and inhibit the ATF4/CREB2 transcription factor that interacts with the basic transcription machinery^[11] and to bind with two human chromosome-associated cellular proteins, MeCP2 and DEK.^[9]

LANA-1 is associated with cellular chromatin and stays on the chromosomes during cell division.^[12] It maintains the viral genomes during cell division by tethering the viral episomes to the chromosomes.^[13] It binds directly to replication origin recognition complexes (ORCs) that are primarily associated with the terminal repeat (TR) region of the HHV-8 genome.^[14]

Notes and references

^ Kedes DH, Lagunoff M, Renne R, Ganem D (November 1997). "Identification of the gene encoding the major latency-associated nuclear antigen of the Kaposi's sarcoma-associated herpesvirus". The Journal of Clinical Investigation 100 (10): 2606–10. doi:10.1172/JCI119804. PMC 508462. PMID 9366576. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=508462.
^ Kellam P, Boshoff C, Whitby D, Matthews S, Weiss RA, Talbot SJ (1997). "Identification of a major latent nuclear antigen, LNA-1, in the human herpesvirus 8 genome". Journal of Human Virology 1 (1): 19–29. PMID 10195227.
^ ^a ^b Rainbow L, Platt GM, Simpson GR, et al. (August 1997). "The 222- to 234-kilodalton latent nuclear protein (LNA) of Kaposi's sarcoma-associated herpesvirus (human herpesvirus 8) is encoded by orf73 and is a component of the latency-associated nuclear antigen". Journal of Virology 71 (8): 5915–21. PMC 191847. PMID 9223481. http://jvi.asm.org/cgi/pmidlookup?view=long&pmid=9223481.
^ Moore PS, Gao S J, Dominguez G, Cesarman E, Lungu O, Knowles DM, Garber R, Pellett PE, McGeoch DJ, Chang, Y. (January 1996). [1] "Primary characterization of a herpesvirus agent associated with Kaposi's sarcoma"]. The Journal of Virology 70 (1): 549–58. PMID 189843. http://jvi.asm.org/cgi/reprint/70/1/549?view=long&pmid=8523568].
^ Friborg J, Kong W, Hottiger MO, Nabel GJ (1999). "p53 inhibition by the LANA protein of KSHV protects against cell death". Nature 402 (6764): 889–94. doi:10.1038/47266. PMID 10622254.
^ ^a ^b Komatsu T, Ballestas ME, Barbera AJ, Kaye KM (March 2002). "The KSHV latency-associated nuclear antigen: a multifunctional protein". Frontiers in Bioscience 7: d726–30. doi:10.2741/komatsu. PMID 11861213.
^ Jeong JH, Orvis J, Kim JW, McMurtrey CP, Renne R, Dittmer DP (April 2004). "Regulation and autoregulation of the promoter for the latency-associated nuclear antigen of Kaposi's sarcoma-associated herpesvirus". The Journal of Biological Chemistry 279 (16): 16822–31. doi:10.1074/jbc.M312801200. PMID 14742422.
^ Garber AC, Hu J, Renne R (July 2002). "Latency-associated nuclear antigen (LANA) cooperatively binds to two sites within the terminal repeat, and both sites contribute to the ability of LANA to suppress transcription and to facilitate DNA replication". The Journal of Biological Chemistry 277 (30): 27401–11. doi:10.1074/jbc.M203489200. PMID 12015325.
^ ^a ^b ^c Krithivas A, Young DB, Liao G, Greene D, Hayward SD (October 2000). "Human herpesvirus 8 LANA interacts with proteins of the mSin3 corepressor complex and negatively regulates Epstein-Barr virus gene expression in dually infected PEL cells". Journal of Virology 74 (20): 9637–45. doi:10.1128/JVI.74.20.9637-9645.2000. PMC 112396. PMID 11000236. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=112396.
^ Schwam DR, Luciano RL, Mahajan SS, Wong L, Wilson AC (September 2000). "Carboxy terminus of human herpesvirus 8 latency-associated nuclear antigen mediates dimerization, transcriptional repression, and targeting to nuclear bodies". Journal of Virology 74 (18): 8532–40. doi:10.1128/JVI.74.18.8532-8540.2000. PMC 116365. PMID 10954554. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=116365.
^ Lim C, Sohn H, Gwack Y, Choe J (November 2000). "Latency-associated nuclear antigen of Kaposi's sarcoma-associated herpesvirus (human herpesvirus-8) binds ATF4/CREB2 and inhibits its transcriptional activation activity". The Journal of General Virology 81 (Pt 11): 2645–52. PMID 11038375. http://vir.sgmjournals.org/cgi/pmidlookup?view=long&pmid=11038375.
^ Szekely L, Chen F, Teramoto N, et al. (June 1998). "Restricted expression of Epstein-Barr virus (EBV)-encoded, growth transformation-associated antigens in an EBV- and human herpesvirus type 8-carrying body cavity lymphoma line". The Journal of General Virology 79 (Pt 6): 1445–52. PMID 9634087. http://vir.sgmjournals.org/cgi/pmidlookup?view=long&pmid=9634087.
^ Ballestas ME, Chatis PA, Kaye KM (April 1999). "Efficient persistence of extrachromosomal KSHV DNA mediated by latency-associated nuclear antigen". Science 284 (5414): 641–4. doi:10.1126/science.284.5414.641. PMID 10213686.
^ Verma SC, Lan K, Choudhuri T, Robertson ES (April 2006). "Kaposi's sarcoma-associated herpesvirus-encoded latency-associated nuclear antigen modulates K1 expression through its cis-acting elements within the terminal repeats". Journal of Virology 80 (7): 3445–58. doi:10.1128/JVI.80.7.3445-3458.2006. PMC 1440413. PMID 16537612. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=1440413.

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1. ヒトヘルペスウイルス8感染の診断および抗ウイルス療法 diagnosis and antiviral therapy of human herpesvirus 8 infection

English Journal

Toys in the upper aerodigestive tract: evidence on their risk as emerging from the ESFBI study.

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Auris, nasus, larynx.Auris Nasus Larynx.2011 Oct;38(5):612-7. Epub 2011 Feb 26.
OBJECTIVE: Foreign body inhalation/aspiration or ingestion is a relatively common event in young children and, despite many efforts made in several Countries to reach acceptable safety levels for products devoted to children, small toys or toy parts are frequently mentioned among risky foreign bodie
PMID 21354730

Alcohol and non-communicable diseases (NCDs): time for a serious international public health effort.

Room R, Rehm J, Parry C.SourceAER Centre for Alcohol Policy Research, Turning Point Alcohol & Drug Centre, Fitzroy, Vic., Australia; School of Population Health, University of Melbourne, Australia and Centre for Social Research on Alcohol and Drugs, Stockholm University, Sweden, Centre for Addiction and Mental Health, Toronto, Canada; Dalla Lana School of Public Health Department of Psychiatry, University of Toronto, Canada and Institut fur Klinische Psychologie und Psychotherapie, Technische Universitat Dresden, Germany Alcohol and Drug Abuse Research Unit, Medical Research Council, South Africa; Department of Psychiatry, Stellenbosch University, South Africa and Global Alcohol Policy Alliance, London, UK. E-mail: robinr@turningpoint.org.au.
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PMID 21815918

Japanese Journal

AIDS患者にみられたKaposi肉腫の1例 (特集ウイルス感染症)

上嶋祐太,萩原藤子,伊藤ゆり子 [他]
皮膚科の臨床 52(12), 1807-1810, 2010-11
NAID 40017371168

Rare Primary Effusion Lymphoma Associated with HHV-8 in Japan

Ikebe Taichi,Amemiya Yuka,Saburi Masuho,Ando Takeaki,Kohno Kazuhiro,Ogata Masao,Hiramatsu Kazufumi,Kadota Junichi
Internal Medicine 49(13), 1303-1306, 2010
… Pleural effusion contained atypical lymphoid cells with human herpesvirus (HHV)-8 latent nuclear antigen (LANA)+. …
NAID 130000299529