Abstract
Post-translational modifications (PTMs) are chemical alterations to individual amino acids that alter a protein’s conformation, stability, and/or function. Several pathogenic viruses have been shown to encode proteins with PTMs, including human T-cell leukemia virus type 1 (HTLV-1) Tax and Rex regulatory proteins. HTLV-1 basic leucine zipper protein (HBZ) was hypothesized to feature PTMs due to its functional activities and interactions with cellular transcription factors and acetyltransferases. Here, we describe the approach used to identify, via mass spectrometry, the PTMs of HBZ. In addition, we describe methods to determine the functional relevance of the identified PTMs.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
References
Poiesz BJ, Ruscetti FW, Gazdar AF et al (1980) Detection and isolation of type C retrovirus particles from fresh and cultured lymphocytes of a patient with cutaneous T-cell lymphoma. Proc Natl Acad Sci U S A 77:7415–7419
Yoshida M, Miyoshi I, Hinuma Y (1982) Isolation and characterization of retrovirus from cell lines of human adult T-cell leukemia and its implication in the disease. Proc Natl Acad Sci U S A 79:2031–2035. doi:10.1186/s12985-015-0398-x
Osame M, Usuku K, Izumo S et al (1986) HTLV-I associated myelopathy, a new clinical entity. Lancet 1:1031–1032
Matsuoka M (2005) Human T-cell leukemia virus type I (HTLV-I) infection and the onset of adult T-cell leukemia (ATL). Retrovirology 2:27. doi:10.1186/1742-4690-2-27
Nicot C, Harrod RL, Ciminale V, Franchini G (2005) Human T-cell leukemia/lymphoma virus type 1 nonstructural genes and their functions. Oncogene 24:6026–6034. doi:10.1038/sj.onc.1208977
Felber BK, Paskalis H, Kleinman-Ewing C et al (1985) The pX protein of HTLV-I is a transcriptional activator of its long terminal repeats. Science 229:675–679
Grassmann R, Berchtold S, Radant I et al (1992) Role of human T-cell leukemia virus type 1 X region proteins in immortalization of primary human lymphocytes in culture. J Virol 66:4570–4575
Grossman WJ, Kimata JT, Wong FH et al (1995) Development of leukemia in mice transgenic for the tax gene of human T-cell leukemia virus type I. Proc Natl Acad Sci U S A 92:1057–1061
Michael D, Robek LR (1999) Immortalization of CD4(+) and CD8(+) T lymphocytes by human T-cell leukemia virus type 1 Tax mutants expressed in a functional molecular clone. J Virol 73:4856–4865
Gaudray G, Gachon F, Basbous J et al (2002) The complementary strand of the human T-cell leukemia virus type 1 RNA genome encodes a bZIP transcription factor that down-regulates viral transcription. J Virol 76:12813–12822. doi:10.1128/JVI.76.24.12813-12822.2002
Larocca D, Chao LA, Seto MH, Brunck TK (1989) Human T-cell leukemia virus minus strand transcription in infected T-cells. Biochem Biophys Res Commun 163:1006–1013
Lemasson I, Lewis MR, Polakowski N et al (2007) Human T-cell leukemia virus type 1 (HTLV-1) bZIP protein interacts with the cellular transcription factor CREB to inhibit HTLV-1 transcription. J Virol 81:1543–1553. doi:10.1128/JVI.00480-06
Basbous J, Arpin C, Gaudray G et al (2003) The HBZ factor of human T-cell leukemia virus type I dimerizes with transcription factors JunB and c-Jun and modulates their transcriptional activity. J Biol Chem 278:43620–43627. doi:10.1074/jbc.M307275200
Zhao T, Yasunaga J-I, Satou Y et al (2009) Human T-cell leukemia virus type 1 bZIP factor selectively suppresses the classical pathway of NF-kappaB. Blood 113:2755–2764. doi:10.1182/blood-2008-06-161729
Mukai R, Ohshima T (2011) Dual effects of HTLV-1 bZIP factor in suppression of interferon regulatory factor 1. Biochem Biophys Res Commun 409:328–332. doi:10.1016/j.bbrc.2011.05.014
Satou Y, Yasunaga J-I, Yoshida M, Matsuoka M (2006) HTLV-I basic leucine zipper factor gene mRNA supports proliferation of adult T cell leukemia cells. Proc Natl Acad Sci U S A 103:720–725. doi:10.1073/pnas.0507631103
Arnold J, Zimmerman B, Li M et al (2008) Human T-cell leukemia virus type-1 antisense-encoded gene, Hbz, promotes T-lymphocyte proliferation. Blood 112:3788–3797. doi:10.1182/blood-2008-04-154286
Satou Y, Yasunaga J-I, Zhao T et al (2011) HTLV-1 bZIP factor induces T-cell lymphoma and systemic inflammation in vivo. PLoS Pathog 7:e1001274. doi:10.1371/journal.ppat.1001274
Takeda S, Maeda M, Morikawa S et al (2004) Genetic and epigenetic inactivation of tax gene in adult T-cell leukemia cells. Int J Cancer 109:559–567. doi:10.1002/ijc.20007
Koiwa T, Hamano-Usami A, Ishida T et al (2002) 5'-long terminal repeat-selective CpG methylation of latent human T-cell leukemia virus type 1 provirus in vitro and in vivo. J Virol 76:9389–9397. doi:10.1128/JVI.76.18.9389-9397.2002
Furukawa Y, Kubota R, Tara M et al (2001) Existence of escape mutant in HTLV-I tax during the development of adult T-cell leukemia. Blood 97:987–993
Prabakaran S, Lippens G, Steen H, Gunawardena J (2012) Post-translational modification: nature's escape from genetic imprisonment and the basis for dynamic information encoding. Wiley Interdiscip Rev Syst Biol Med 4:565–583. doi:10.1002/wsbm.1185
Bex F, Murphy K, Wattiez R et al (1999) Phosphorylation of the human T-cell leukemia virus type 1 transactivator tax on adjacent serine residues is critical for tax activation. J Virol 73:738–745
Lodewick J, Lamsoul I, Polania A et al (2009) Acetylation of the human T-cell leukemia virus type 1 Tax oncoprotein by p300 promotes activation of the NF-κB pathway. Virology 386:68–78. doi:10.1016/j.virol.2008.12.043
Fryrear KA, Guo X, Kerscher O, Semmes OJ (2012) The Sumo-targeted ubiquitin ligase RNF4 regulates the localization and function of the HTLV-1 oncoprotein Tax. Blood 119:1173–1181. doi:10.1182/blood-2011-06-358564
Kesic M, Doueiri R, Ward M et al (2009) Phosphorylation regulates human T-cell leukemia virus type 1 Rex function. Retrovirology 6:105. doi:10.1186/1742-4690-6-105
Matsumoto J, Ohshima T, Isono O, Shimotohno K (2005) HTLV-1 HBZ suppresses AP-1 activity by impairing both the DNA-binding ability and the stability of c-Jun protein. Oncogene 24:1001–1010. doi:10.1038/sj.onc.1208297
Zhi H, Yang L, Kuo Y-L et al (2011) NF-κB hyper-activation by HTLV-1 Tax induces cellular senescence, but can be alleviated by the viral anti-sense protein HBZ. PLoS Pathog 7:e1002025. doi:10.1371/journal.ppat.1002025.g007
Kelly JJ, Shao Q, Jagger DJ, Laird DW (2015) Cx30 exhibits unique characteristics including a long half-life when assembled into gap junctions. J Cell Sci 128(21):3947–3960. doi:10.1242/jcs.174698
Author information
Authors and Affiliations
Corresponding author
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2017 Springer Science+Business Media LLC
About this protocol
Cite this protocol
Al-Saleem, J., Kvaratskhelia, M., Green, P.L. (2017). Methods for Identifying and Examining HTLV-1 HBZ Post-translational Modifications. In: Casoli, C. (eds) Human T-Lymphotropic Viruses. Methods in Molecular Biology, vol 1582. Humana Press, New York, NY. https://doi.org/10.1007/978-1-4939-6872-5_9
Download citation
DOI: https://doi.org/10.1007/978-1-4939-6872-5_9
Published:
Publisher Name: Humana Press, New York, NY
Print ISBN: 978-1-4939-6870-1
Online ISBN: 978-1-4939-6872-5
eBook Packages: Springer Protocols