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  • Original Paper
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Physical interaction of the bHLH LYL1 protein and NF-κB1 p105

Abstract

The LYL1 gene was first identified upon the molecular characterization of the t(7;9)(q35;p13) translocation associated with some human T-cell acute leukemias (T-ALLs). In adult tissues, LYL1 expression is restricted to hematopoietic cells with the notable exclusion of the T cell lineage. LYL1 encodes a basic helix – loop – helix (bHLH) protein highly related to TAL-1, whose activation is also associated with a high proportion of human T-ALLs. A yeast two-hybrid system was used to identify proteins that specifically interact with LYL1 and might mediate its activities. We found that p105, the precursor of NF-κB1 p50, was the major LYL1-interacting protein in this system. The association between LYL1 and p105 was confirmed both in vitro and in vivo in mammalian cells. Biochemical studies indicated that the interaction was mediated by the bHLH motif of LYL1 and the ankyrin-like motifs of p105. Ectopic expression of LYL1 in a human T cell line caused a significant decrease in NF-κB-dependent transcription, associated with a reduced level of NF-κB1 proteins.

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Acknowledgements

We are grateful to Urszula Hibner, Naomi Taylor and Robert Hipskind for helpful discussion and critical comments on the manuscript. We greatly appreciate Cécile Lambert for her excellent technical assistance. We are greatly indebted to Alain Israel (Institut Pasteur, Paris, France) for providing us with the (Igκ)3-conaluc plasmid and the anti p50/p105 antibody, to Michael Clearly and Alison Miyamoto (Stanford University, School of Medecine, USA) for the anti LYL1 antibody, to Jacques Camonis (Institut Curie, Paris, France) for the Jurkat cDNA library, to Marc-Henri Stern (Hôpital Saint Louis, Paris, France) for the pGAD-I-κBα plasmid, Brigitte Royer-Pokora (Heidelberg, Germany) for the Lmo2/TTG2 cDNA and JM Blanchard (Montpellier, France) for the anti GAPDH antibody. This work was supported in part by grants from the `Association pour la Recherche sur le Cancer' (ARC), the `Ligue Nationale contre le Cancer' and the `Fondation contre la Leucémie'. RF is supported by a fellowship from the `Association pour la Recherche sur le Cancer' (ARC).

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Ferrier, R., Nougarede, R., Doucet, S. et al. Physical interaction of the bHLH LYL1 protein and NF-κB1 p105. Oncogene 18, 995–1005 (1999). https://doi.org/10.1038/sj.onc.1202374

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