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Journal of Virology, August 2008, p. 7913-7922, Vol. 82, No. 16
0022-538X/08/$08.00+0 doi:10.1128/JVI.02414-07
Copyright © 2008, American Society for Microbiology. All Rights Reserved.
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Laboratoire de Biologie Moléculaire de la Cellule, UMR5239 CNRS/ENS de Lyon, IFR 128 Biosciences Lyon Gerland, 46 Allée d'Italie, 69364 Lyon cedex 07, France,1 INSERM-U758 Virologie Humaine, ENS de Lyon, IFR 128 Biosciences Lyon Gerland, 46 Allée d'Italie, 69364 Lyon cedex 07, France,2 Institut de Recherches Microbiologiques J-M Wiame, Laboratoire de Microbiologie ULB/CERIA Batiment 4B, 2ème étage, 1, Avenue E. Gryson, B-1070 Brussels, Belgium3
Received 8 November 2007/ Accepted 15 May 2008
The human T-cell leukemia virus type 1 (HTLV-1) Tax transactivator is known to induce or repress various cellular genes, several of them encoding transcription factors. As Tax is known to deregulate various basic bHLH factors, we looked more specifically at its effect on TAL1 (T-cell acute lymphoblastic leukemia 1), also known as SCL (stem cell leukemia). Indeed, TAL1 is deregulated in a high percentage of T-cell acute lymphoblastic leukemia cells, and its oncogenic properties are well-established. Here we show that Tax induces transcription of this proto-oncogene by stimulating the activity of the TAL1 gene promoter 1b, through both the CREB and NF-
B pathways. It was also observed that TAL1 upregulates HTLV-1 promoter activity, in either the presence or the absence of Tax. The viral promoter is inhibited in trans by expression of the E2A protein E47, and TAL1 is able to abrogate this inhibition. These data show the existence of a positive feedback loop between Tax and TAL1 expression and support the notion that this proto-oncogene participates in generation of adult T-cell leukemia/lymphoma by increasing the amount of the Tax oncoprotein but also possibly by its own transforming activities.
Published ahead of print on 21 May 2008.
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