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

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

Research output: Contribution to journalArticle

15 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)1401-1409
Number of pages9
JournalOncogene
Volume18
Issue number7
DOIs
StatePublished - Feb 18 1999

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Deltaretrovirus
T-Lymphocytes
Interleukin-2
Growth
Transcription Factors
Cell Proliferation
Adult T Cell Leukemia Lymphoma
Human T-lymphotropic virus 1
Reporter Genes
Transcriptional Activation
Genes
Blood Cells
Neoplasms

All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Genetics
  • Cancer Research

Cite this

Sun, Shao Cong ; Maggirwar, Sanjay B. ; Harhaj, Edward W. ; Uhlik, Mark. / Binding of c-Rel to STAT5 target sequences in HTLV-I-transformed T cells. In: Oncogene. 1999 ; Vol. 18, No. 7. pp. 1401-1409.
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Binding of c-Rel to STAT5 target sequences in HTLV-I-transformed T cells. / Sun, Shao Cong; Maggirwar, Sanjay B.; Harhaj, Edward W.; Uhlik, Mark.

In: Oncogene, Vol. 18, No. 7, 18.02.1999, p. 1401-1409.

Research output: Contribution to journalArticle

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