Abstract
RNA helicase A (RHA) containing the DExH motif is a human homolog of maleless protein that regulates expression of genes located in the Drosophila X chromosome during dosage compensation. RHA exerts helicase activity that unwinds double-stranded RNA and DNA to a single-strand form. The protein acts as a bridging factor mediating interactions of CBP/p300 and RNA pol II, and consequently affects gene expression. Kaposi’s sarcoma-associated herpesvirus (KSHV) is a member of the γ-herpesvirus subfamily that causes several disorders. The majority of herpesviruses commonly encode predicted viral protein kinases. KSHV open reading frame 36 (ORF36) codes for protein kinase domains, and functions as a serine/threonine protein kinase. KSHV ORF36 is classified as a late gene, as it is expressed during lytic replication and localized in the nuclei of KSHV-infected cells. Recent studies show that viral protein kinase (vPK) interacts with cellular proteins. In this study, we determined the cellular localization of vPK in KSHV-infected BCBL-1 cells using confocal microscopy. Proteomic analysis indicates that cellular proteins interacted with vPK, and co-immunoprecipitation reactions further reveal interactions between vPK and RHA. Moreover, KSHV vPK appeared to regulate the transcriptional activation of Cre promoter, and plays an important role in cellular transcription of RHA.
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Anderson, S.F., B.P. Schlegel, T. Nakajima, E.S. Wolpin, and J.D. Parvin. 1998. Brca1 protein is linked to the RNA polymerase ii holoenzyme complex via RNA helicase A. Nat. Genet. 19, 254–256.
Aratani, S., R. Fujii, T. Oishi, H. Fujita, T. Amano, T. Ohshima, M. Hagiwara, A. Fukamizu, and T. Nakajima. 2001. Dual roles of RNA helicase a in CREB-dependent transcription. Mol. Cell. Biol. 21, 4460–4469.
Aratani, S., T. Oishi, H. Fujita, M. Nakazawa, R. Fujii, N. Imamoto, Y. Yoneda, A. Fukamizu, and T. Nakajima. 2006. The nuclear import of RNA helicase a is mediated by importin-alpha3. Biochem. Biophys. Res. Commun. 340, 125–133.
Arvanitakis, L., E. Geras-Raaka, A. Varma, M.C. Gershengorn, and E. Cesarman. 1997. Human herpesvirus KSHV encodes a constitutively active G-protein-coupled receptor linked to cell proliferation. Nature 385, 347–350.
Bannister, A.J. and T. Kouzarides. 1996. The CBP co-activator is a histone acetyltransferase. Nature 384, 641–643.
Cathomas, G. 2003. Kaposi’s sarcoma-associated herpesvirus (KSHV)/human herpesvirus 8 (HHV-8) as a tumour virus. Herpes. 10, 72–77.
Cesarman, E., Y. Chang, P.S. Moore, J.W. Said, and D.M. Knowles. 1995. Kaposi’s sarcoma-associated herpesvirus-like DNA sequences in aids-related body-cavity-based lymphomas. N. Engl. J. Med. 332, 1186–1191.
Chang, Y., E. Cesarman, M.S. Pessin, F. Lee, J. Culpepper, D.M. Knowles, and P.S. Moore. 1994. Identification of herpesvirus-like DNA sequences in aids-associated Kaposi’s sarcoma. Science 266, 1865–1869.
Decker, L.L., P. Shankar, G. Khan, R.B. Freeman, B.J. Dezube, J. Lieberman, and D.A. Thorley-Lawson. 1996. The kaposi sarcomaassociated herpesvirus (KSHV) is present as an intact latent genome in KS tissue but replicates in the peripheral blood mononuclear cells of KS patients. J. Exp. Med. 184, 283–288.
Della Fazia, M.A., G. Servillo, and P. Sassone-Corsi. 1997. Cyclic AMP signalling and cellular proliferation: Regulation of CREB and CREM. FEBS Lett. 410, 22–24.
Deng, H., Y. Liang, and R. Sun. 2007. Regulation of KSHV lytic gene expression. Curr. Top Microbiol. Immunol. 312, 157–183.
Fujita, H., T. Ohshima, T. Oishi, S. Aratani, R. Fujii, A. Fukamizu, and T. Nakajima. 2005. Relevance of nuclear localization and functions of RNA helicase A. Int. J. Mol. Med. 15, 555–560.
Fuller-Pace, F.V. 2006. DExD/H box RNA helicases: Multifunctional proteins with important roles in transcriptional regulation. Nucleic Acids Res. 34, 4206–4215.
Hamza, M.S., R.A. Reyes, Y. Izumiya, R. Wisdom, H.J. Kung, and P.A. Luciw. 2004. Orf36 protein kinase of Kaposi’s sarcoma herpesvirus activates the c-Jun N-terminal kinase signaling pathway. J. Biol. Chem. 279, 38325–38330.
Hwang, S., K.S. Kim, E. Flano, T.T. Wu, L.M. Tong, A.N. Park, M.J. Song, D.J. Sanchez, R.M. O’Connell, G. Cheng, and R. Sun. 2009. Conserved herpesviral kinase promotes viral persistence by inhibiting the IRF-3-mediated type I interferon response. Cell Host Microbe 5, 166–178.
Izumiya, Y., C. Izumiya, A. Van Geelen, D.H. Wang, K.S. Lam, P.A. Luciw, and H.J. Kung. 2007. Kaposi’s sarcoma-associated herpesvirusencoded protein kinase and its interaction with K-bZIP. J. Virol. 81, 1072–1082.
Kawaguchi, Y. and K. Kato. 2003. Protein kinases conserved in herpesviruses potentially share a function mimicking the cellular protein kinase cdc2. Rev. Med. Virol. 13, 331–340.
Lee, C.G. and J. Hurwitz. 1992. A new RNA helicase isolated from hela cells that catalytically translocates in the 3′ to 5′ direction. J. Biol. Chem. 267, 4398–4407.
Lee, C.G. and J. Hurwitz. 1993. Human RNA helicase a is homologous to the maleless protein of drosophila. J. Biol. Chem. 268, 16822–16830.
Linder, P., P.F. Lasko, M. Ashburner, P. Leroy, P.J. Nielsen, K. Nishi, J. Schnier, and P.P. Slonimski. 1989. Birth of the d-e-a-d box. Nature 337, 121–122.
Liu, Z., R. Kenworthy, C. Green, and H. Tang. 2007. Molecular determinants of nucleolar translocation of RNA helicase A. Exp. Cell Res. 313, 3743–3754.
Lukac, D.M., R. Renne, J.R. Kirshner, and D. Ganem. 1998. Reactivation of Kaposi’s sarcoma-associated herpesvirus infection from latency by expression of the ORF 50 transactivator, a homolog of the EBV R protein. Virology 252, 304–312.
Mullan, P.B., J.E. Quinn, and D.P. Harkin. 2006. The role of BRCA1 in transcriptional regulation and cell cycle control. Oncogene 25, 5854–5863.
Nakajima, T., C. Uchida, S.F. Anderson, C.G. Lee, J. Hurwitz, J.D. Parvin, and M. Montminy. 1997a. RNA helicase a mediates association of CBP with RNA polymerase II. Cell 90, 1107–1112.
Nakajima, T., C. Uchida, S.F. Anderson, J.D. Parvin, and M. Montminy. 1997b. Analysis of a camp-responsive activator reveals a two-component mechanism for transcriptional induction via signal-dependent factors. Genes Dev. 11, 738–747.
Neipel, F., J.C. Albrecht, A. Ensser, Y.Q. Huang, J.J. Li, A.E. Friedman-Kien, and B. Fleckenstein. 1997. Human herpesvirus 8 encodes a homolog of interleukin-6. J. Virol. 71, 839–842.
Park, J., D. Lee, T. Seo, J. Chung, and J. Choe. 2000. Kaposi’s sarcoma-associated herpesvirus (human herpesvirus-8) open reading frame 36 protein is a serine protein kinase. J. Gen. Virol. 81, 1067–1071.
Park, J., M.S. Lee, S.M. Yoo, and T. Seo. 2007. A novel protein encoded by Kaposi’s sarcoma-associated herpesvirus open reading frame 36 inhibits cell spreading and focal adhesion kinase activation. Intervirology 50, 426–432.
Parravicini, C., B. Chandran, M. Corbellino, E. Berti, M. Paulli, P.S. Moore, and Y. Chang. 2000. Differential viral protein expression in Kaposi’s sarcoma-associated herpesvirus-infected diseases: Kaposi’s sarcoma, primary effusion lymphoma, and multicentric castleman’s disease. Am. J. Pathol. 156, 743–749.
Reddy, T.R., H. Tang, W. Xu, and F. Wong-Staal. 2000. Sam68, RNA helicase a and tap cooperate in the post-transcriptional regulation of human immunodeficiency virus and type d retroviral mRNA. Oncogene 19, 3570–3575.
Roizman, B., L.E. Carmichael, F. Deinhardt, G. de-The, A.J. Nahmias, W. Plowright, F. Rapp, P. Sheldrick, M. Takahashi, and K. Wolf. 1981. Herpesviridae. Definition, provisional nomenclature, and taxonomy. The herpesvirus study group, the international committee on taxonomy of viruses. Intervirology 16, 201–217.
Russo, J.J., R.A. Bohenzky, M.C. Chien, J. Chen, M. Yan, D. Maddalena, J.P. Parry, D. Peruzzi, I.S. Edelman, Y. Chang, and P.S. Moore. 1996. Nucleotide sequence of the Kaposi sarcoma-associated herpesvirus (HHV8). Proc. Natl. Acad. Sci. USA 93, 14862–14867.
Shaywitz, A.J. and M.E. Greenberg. 1999. Creb: A stimulus-induced transcription factor activated by a diverse array of extracellular signals. Annu. Rev. Biochem. 68, 821–861.
Smith, W.A., B.T. Schurter, F. Wong-Staal, and M. David. 2004. Arginine methylation of RNA helicase a determines its subcellular localization. J. Biol. Chem. 279, 22795–22798.
Smith, R.F. and T.F. Smith. 1989. Identification of new protein kinase-related genes in three herpesviruses, herpes simplex virus, varicella-zoster virus, and epstein-barr virus. J. Virol. 63, 450–455.
Soulier, J., L. Grollet, E. Oksenhendler, P. Cacoub, D. Cazals-Hatem, P. Babinet, M.F. d’Agay, and et al. 1995. Kaposi’s sarcoma-associated herpesvirus-like DNA sequences in multicentric castleman’s disease. Blood 86, 1276–1280.
Tang, H. and F. Wong-Staal. 2000. Specific interaction between RNA helicase A and tap, two cellular proteins that bind to the constitutive transport element of type D retrovirus. J. Biol. Chem. 275, 32694–32700.
Tanner, N.K. and P. Linder. 2001. DExD/H box RNA helicases: From generic motors to specific dissociation functions. Mol. Cell. 8, 251–262.
Yu, Y., J.B. Black, C.S. Goldsmith, P.J. Browning, K. Bhalla, and M.K. Offermann. 1999. Induction of human herpesvirus-8 DNA replication and transcription by butyrate and TPA in BCBL-1 cells. J. Gen. Virol. 80, 83–90.
Zhang, S. and F. Grosse. 1994. Nuclear DNA helicase II unwinds both DNA and RNA. Biochemistry 33, 3906–3912.
Zhang, S. and F. Grosse. 2004. Multiple functions of nuclear DNA helicase II (RNA helicase A) in nucleic acid metabolism. Acta. Biochim. Biophys. Sin. (Shanghai) 36, 177–183.
Zhang, S., B. Schlott, M. Gorlach, and F. Grosse. 2004. DNA-dependent protein kinase (DNA-pk) phosphorylates nuclear DNA helicase II/RNA helicase A and hnrnp proteins in an RNA-dependent manner. Nucleic Acids Res. 32, 1–10.
Zhong, X. and A.R. Safa. 2007. Phosphorylation of RNA helicase a by DNA-dependent protein kinase is indispensable for expression of the MDR1 gene product P-glycoprotein in multidrug-resistant human leukemia cells. Biochemistry 46, 5766–5775.
Zhong, W., H. Wang, B. Herndier, and D. Ganem. 1996. Restricted expression of kaposi sarcoma-associated herpesvirus (human herpesvirus 8) genes in kaposi sarcoma. Proc. Natl. Acad. Sci. USA 93, 6641–6646.
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Jong, J.E., Park, J., Kim, S. et al. Kaposi’s sarcoma-associated herpesvirus viral protein kinase interacts with RNA helicase a and regulates host gene expression. J Microbiol. 48, 206–212 (2010). https://doi.org/10.1007/s12275-010-0021-1
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DOI: https://doi.org/10.1007/s12275-010-0021-1