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 leukemiavirus 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 deregulatevarious basic bHLH factors, we looked more specifically at its effect on TAL1(T-cell acute lymphoblastic leukemia1), also known as SCL (stem cell leukemia). Indeed, TAL1is deregulatedin a high percentage of T-cell acute lymphoblastic leukemiacells, and its oncogenicproperties are well-established. Here we show that Tax induces transcription of this proto- oncogeneby stimulating the activity of the TAL1gene promoter 1b, through both the CREBand NF-κB pathways. It was also observed that TAL1upregulates 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 TAL1is able to abrogate this inhibition. These data show the existence of a positive feedback loop between Tax and TAL1expression and support the notion that this proto- oncogeneparticipates in generation of adult T-cell leukemia/lymphomaby increasing the amount of the Tax oncoprotein but also possibly by its own transforming activities.