Crosstalk between expression of the HTLV-1 Tax transactivator and the oncogenic bHLH transcription factor TAL1

Authors:
Terme JM, Wencker M, Favre-Bonvin A, Bex F, Gazzolo L, Duc Dodon M, Jalinot P
In:
Source: J Virol
Publication Date: (2008)
Issue: 82(16): 7913-22
Research Area:
Immunotherapy / Hematology
Cells used in publication:
Jurkat
Species: human
Tissue Origin: blood
Platform:
Nucleofectorâ„¢ I/II/2b
Abstract
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 bHLH factors, we looked more specifically at its effect on TAL1 (T-cell acute lymphoblastic leukemia 1), also known as Stem cell leukemia (SCL). Indeed, TAL1 is deregulated in a high percentage of T-cell Acute Lymphoblastic Leukemia (T-ALL) and its oncogenic properties are well-established. Here we show that Tax induces transcription of this protooncogene 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 the activity of HTLV-1 promoter activity, either in 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 protoncogene participates to ATL generation by increasing the amount of the Tax oncoprotein, but also possibly by its own transforming activities.