Human T-Cell Lymphotropic Virus Type 1 Tax Represses c-Myb-Dependent Transcription through Activation of the NF-{kappa}B Pathway and Modulation of Coactivator Usage

doi:10.1128/MCB.21.21.7391-7402.2001

This Article

	Full Text
	Full Text (PDF)
	Alert me when this article is cited
	Alert me if a correction is posted

Services

	Similar articles in this journal
	Similar articles in PubMed
	Alert me to new issues of the journal
	Download to citation manager
	Reprints and Permissions
	Copyright Information
	Books from ASM Press
	MicrobeWorld

Citing Articles

	Citing Articles via HighWire
	Citing Articles via Google Scholar

Google Scholar

	Articles by Nicot, C.
	Articles by Franchini, G.
	Search for Related Content

PubMed

	PubMed Citation
	Articles by Nicot, C.
	Articles by Franchini, G.

Previous Article | Next Article

Molecular and Cellular Biology, November 2001, p. 7391-7402, Vol. 21, No. 21
0270-7306/01/$04.00+0 DOI: 10.1128/MCB.21.21.7391-7402.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.

Human T-Cell Lymphotropic Virus Type 1 Tax Represses c-Myb-Dependent Transcription through Activation of the NF- $kappa$ B Pathway and Modulation of Coactivator Usage

Christophe Nicot,¹^,^* Renaud Mahieux,² Cynthia Pise-Masison,³ John Brady,³ Antoine Gessain,² Shoji Yamaoka,⁴ and Genoveffa Franchini¹

Section of Animal Models and Retroviral Vaccines¹ and Section of Virus and Tumor Biology,³ Basic Research Laboratory, Center for Cancer Research, National Cancer Institute, Bethesda, Maryland 20892; Unite d'Epidemiologie et Physiopathologie des Virus Oncogenes, Institut Pasteur, 75724 Paris cedex 15, France²; and Department of Microbiology, Tokyo Medical and Dental University, Bunkyo-ku, 113-8519 Tokyo, Japan⁴

Received 25 June 2001/Returned for modification 6 August 2001/Accepted 10 August 2001

The proto-oncogene c-myb is essential for a controlled balance between cell growth and differentiation. Aberrant c-Myb activityhas been reported for numerous human cancers, and enforced c-Mybtranscription can transform cells of lymphoid origin by stimulatingcellular proliferation and inhibiting apoptotic pathways. Herewe demonstrate that activation of the NF- $kappa$ B pathway by the HTLV-1Tax protein leads to transcriptional inactivation of c-Myb. Thisconclusion was supported by the fact that Tax mutants unable tostimulate the NF- $kappa$ B pathway could not inhibit c-Myb transactivatingfunctions. In addition, inhibition of Tax-mediated NF- $kappa$ B activationby coexpression of I $kappa$ B $alpha$ restored c-Myb transcription, and Taxwas unable to block c-Myb transcription in a NEMO knockout cellline. Importantly, physiological stimuli, such as signaling withthe cellular cytokines tumor necrosis factor alpha, interleukin1 beta (IL-1 $beta$ ), and lipopolysaccharide, also inhibited c-Myb transcription.These results uncover a new link between extracellular signalingand c-Myb-dependent transcription. The mechanism underlying NF- $kappa$ B-mediatedrepression was identified as sequestration of the coactivatorsCBP/p300 by RelA. Interestingly, an amino-terminal deletion formof p300 lacking the C/H1 and KIX domains and unable to bind RelAretained the ability to stimulate c-Myb transcription and preventedNF- $kappa$ B-mediatedrepression.

^* Corresponding author. Mailing address: NCI Ctr. for Cancer Research BRL, Section of Animal Models and Retroviral Vaccines,41 Library Dr., Bldg. 41, Room C303, Bethesda, MD 20892. Phone:(301) 402-0303. Fax: (301) 402-0055. E-mail: cbeben{at}helix.nih.gov.

This article has been cited by other articles:

Chin, K.-T., Chun, A. C.S., Ching, Y.-P., Jeang, K.-T., Jin, D.-Y. (2007). Human T-Cell Leukemia Virus Oncoprotein Tax Represses Nuclear Receptor-Dependent Transcription by Targeting Coactivator TAX1BP1. Cancer Res. 67: 1072-1081 [Abstract] [Full Text]
Ghorbel, S., Sinha-Datta, U., Dundr, M., Brown, M., Franchini, G., Nicot, C. (2006). Human T-cell Leukemia Virus Type I p30 Nuclear/Nucleolar Retention Is Mediated through Interactions with RNA and a Constituent of the 60 S Ribosomal Subunit. J. Biol. Chem. 281: 37150-37158 [Abstract] [Full Text]
Datta, A., Sinha-Datta, U., Dhillon, N. K., Buch, S., Nicot, C. (2006). The HTLV-I p30 Interferes with TLR4 Signaling and Modulates the Release of Pro- and Anti-inflammatory Cytokines from Human Macrophages. J. Biol. Chem. 281: 23414-23424 [Abstract] [Full Text]
Tabakin-Fix, Y., Azran, I., Schavinky-Khrapunsky, Y., Levy, O., Aboud, M. (2006). Functional inactivation of p53 by human T-cell leukemia virus type 1 Tax protein: mechanisms and clinical implications. Carcinogenesis 27: 673-681 [Abstract] [Full Text]
Awasthi, S., Sharma, A., Wong, K., Zhang, J., Matlock, E. F., Rogers, L., Motloch, P., Takemoto, S., Taguchi, H., Cole, M. D., Luscher, B., Dittrich, O., Tagami, H., Nakatani, Y., McGee, M., Girard, A.-M., Gaughan, L., Robson, C. N., Monnat, R. J. Jr., Harrod, R. (2005). A Human T-Cell Lymphotropic Virus Type 1 Enhancer of Myc Transforming Potential Stabilizes Myc-TIP60 Transcriptional Interactions. Mol. Cell. Biol. 25: 6178-6198 [Abstract] [Full Text]
Jeong, S.-J., Radonovich, M., Brady, J. N., Pise-Masison, C. A. (2004). HTLV-I Tax induces a novel interaction between p65/RelA and p53 that results in inhibition of p53 transcriptional activity. Blood 104: 1490-1497 [Abstract] [Full Text]
Lu, H., Pise-Masison, C. A., Linton, R., Park, H. U., Schiltz, R. L., Sartorelli, V., Brady, J. N. (2004). Tax Relieves Transcriptional Repression by Promoting Histone Deacetylase 1 Release from the Human T-Cell Leukemia Virus Type 1 Long Terminal Repeat. J. Virol. 78: 6735-6743 [Abstract] [Full Text]
Vasudevan, K. M., Gurumurthy, S., Rangnekar, V. M. (2004). Suppression of PTEN Expression by NF-{kappa}B Prevents Apoptosis. Mol. Cell. Biol. 24: 1007-1021 [Abstract] [Full Text]
Twizere, J.-C., Kruys, V., Lefebvre, L., Vanderplasschen, A., Collete, D., Debacq, C., Lai, W. S., Jauniaux, J.-C., Bernstein, L. R., Semmes, O. J., Burny, A., Blackshear, P. J., Kettmann, R., Willems, L. (2003). Interaction of Retroviral Tax Oncoproteins With Tristetraprolin and Regulation of Tumor Necrosis Factor-{alpha} Expression. JNCI J Natl Cancer Inst 95: 1846-1859 [Abstract] [Full Text]
Jiang, H. Y., Petrovas, C., Sonenshein, G. E. (2002). RelB-p50 NF-{kappa}B Complexes Are Selectively Induced by Cytomegalovirus Immediate-Early Protein 1: Differential Regulation of Bcl-xL Promoter Activity by NF-{kappa}B Family Members. J. Virol. 76: 5737-5747 [Abstract] [Full Text]

J. Bacteriol.	J. Virol.	Eukaryot. Cell

Microbiol. Mol. Biol. Rev.	Clin. Vaccine Immunol.	All ASM Journals

Human T-Cell Lymphotropic Virus Type 1 Tax Represses c-Myb-Dependent Transcription through Activation of the NF-B Pathway and Modulation of Coactivator Usage

Human T-Cell Lymphotropic Virus Type 1 Tax Represses c-Myb-Dependent Transcription through Activation of the NF- $kappa$ B Pathway and Modulation of Coactivator Usage