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Binding of c-Rel to STAT5 target sequences in HTLV-I-transformed T cells

Oncogene volume 18, pages 1401–1409 (1999)Cite this article

Abstract

The type I human T-cell leukemia virus (HTLV-I) induces abnormal growth and subsequent transformation of T cells, which is associated with the development of an acute T-cell malignancy termed adult T-cell leukemia. A characteristic of HTLV-I-transformed T cells is the constitutive nuclear expression of NF-κB/Rel family of transcription factors, which appears to be essential for the growth of these transformed cells. Although NF-κB/Rel factors are known to induce the expression of T-cell growth factor interleukin (IL)-2, it is unclear how they participate in the IL-2-independent growth of HTLV-I-transformed cells. In this study, we show that certain NF-κB/Rel members, predominantly c-Rel, interact with enhancer sequences for STAT5, a key transcription factor mediating IL-2-induced T-cell proliferation. Reporter gene assays reveal that the binding of c-Rel to the STAT5 site present in the FcγR1 gene leads to potent transactivation of this enhancer. Binding of c-Rel to the FcγR1 STAT site also occurs in human peripheral blood T cells immortalized with HTLV-I in vitro and is correlated with enhanced levels of proliferation of these cells. These results raise the possibility that NF-κB/Rel may participate in the growth control of HTLV-I-transformed T cells by regulating genes driven by both κB and certain STAT enhancers.

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Acknowledgements

We thank T Hirano for GRR-luc reporter, WC Greene for c-Rel cDNA expression vectors. EWH is supported by an NIH predoctoral training grant 5 T32 CA 6039-5. This study was Supported by Public Health Service grant 1 R01 CA68471-03 to SCS.

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  1. Sanjay B Maggirwar

    Present address: Department of Microbiology and Immunology, University of Rochester Medical Center, 575 Elmwood Avenue, Box 672, Rochester, NY14642, USA

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  1. Department of Microbiology and Immunology, Pennsylvania State University College of Medicine, Hershey Medical Center, PO Box 850, Hershey, 17033, Pennsylvania, USA

    Shao-Cong Sun, Sanjay B Maggirwar, Edward W Harhaj & Mark Uhlik

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Sun, SC., Maggirwar, S., Harhaj, E. et al. Binding of c-Rel to STAT5 target sequences in HTLV-I-transformed T cells. Oncogene 18, 1401–1409 (1999). https://doi.org/10.1038/sj.onc.1202430

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