Cross talk between expression of the human T-cell leukemia virus type 1 Tax transactivator and the oncogenic bHLH transcription factor TAL1.
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-kappaB 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.
Terme
Jean-Michel
JM
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.
Wencker
Melanie
M
Favre-Bonvin
Arnaud
A
Bex
Françoise
F
Gazzolo
Louis
L
Duc Dodon
Madeleine
M
Jalinot
Pierre
P
D051792:Basic Helix-Loop-Helix Proteins / Q000378:metabolism*; D001665:Binding Sites; D002460:Cell Line; D025461:Feedback, Physiological; D015967:Gene Expression Regulation, Viral; D016356:Gene Products, tax / Q000378:metabolism*; D006367:HeLa Cells; D015368:Human T-lymphotropic virus 1 / Q000378:metabolism*; D006801:Humans; D015459:Leukemia-Lymphoma, Adult T-Cell / Q000821:virology*; D008954:Models, Biological; D016328:NF-kappa B / Q000378:metabolism; D011401:Promoter Regions, Genetic; D000090063:Proto-Oncogene Mas; D011518:Proto-Oncogene Proteins / Q000378:metabolism*; D000073942:T-Cell Acute Lymphocytic Leukemia Protein 1; D013950:Thymus Gland / Q000166:cytology
D051792:Basic Helix-Loop-Helix Proteins; D016356:Gene Products, tax; D016328:NF-kappa B; D000090063:Proto-Oncogene Mas; D011518:Proto-Oncogene Proteins; D000073942:T-Cell Acute Lymphocytic Leukemia Protein 1; C000715470:MAS1 protein, human; C514970:tax protein, Human T-lymphotrophic virus 1; C067143:TAL1 protein, human