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FOXP3 can modulate TAL1 transcriptional activity through interaction with LMO2

Oncogene volume 35, pages 4141–4148 (2016)Cite this article

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Abstract

T-cell acute lymphoblastic leukemia (T-ALL) frequently involves aberrant expression of TAL1 (T-cell acute lymphocytic leukemia 1) and LMO2, oncogenic members of the TAL1 transcriptional complex. Transcriptional activity of the TAL1-complex is thought to have a pivotal role in the transformation of thymocytes and is associated with a differentiation block and self-renewal. The transcription factor Forkhead Box P3 (FOXP3) was recently described to be expressed in a variety of malignancies including T-ALL. Here we show that increased FOXP3 levels negatively correlate with expression of genes regulated by the oncogenic TAL1-complex in human T-ALL patient samples as well as a T-ALL cell line ectopically expressing FOXP3. In these cells, FOXP3 expression results in altered regulation of cell cycle progression and reduced cell viability. Finally, we demonstrate that FOXP3 binds LMO2 in vitro, resulting in decreased interaction between LMO2 and TAL1, providing a molecular mechanism for FOXP3-mediated transcriptional modulation in T-ALL. Collectively, our findings provide initial evidence for a novel role of FOXP3 as a tumor suppressor in T-ALL through modulation of TAL1 transcriptional activity.

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Acknowledgements

We thank S Sakaguchi and T Mutis for providing us with plasmids and T Radstake for providing us with cells. VF and JvL were supported by a grant from the Dutch Arthritis Foundation (Rheumafonds), and BAC was supported by a fellowship from Fundação para a Ciência e a Tecnologia. This work was supported by grant from the Dutch Arthritis Foundation (Rheumafonds), and a fellowship from Fundação para a Ciência e a Tecnologia.

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Authors and Affiliations

  1. Department of Cell Biology, Centre of Molecular Medicine, University Medical Centre Utrecht, Utrecht, The Netherlands

    V Fleskens, A M van der Leun, S Huppelschoten, C E G M Pals, J Peeters, S Coenen, J van Loosdregt & P J Coffer

  2. Division of Pediatrics, Wilhelmina Children's Hospital, Utrecht, The Netherlands

    M Mokry, J van Loosdregt & P J Coffer

  3. Instituto de Medicina Molecular, Faculdade de Medicina da Universidade de Lisboa, Lisbon, Portugal

    B A Cardoso & J T Barata

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  1. V Fleskens
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Correspondence to P J Coffer.

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Fleskens, V., Mokry, M., van der Leun, A. et al. FOXP3 can modulate TAL1 transcriptional activity through interaction with LMO2. Oncogene 35, 4141–4148 (2016). https://doi.org/10.1038/onc.2015.481

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