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

The type I human T-cell leukemia virus (HTLV-I) induces abnormal growth and subsequent transformation of T cells, which is associated with the develop ment of an acute T-cell malignancy termed adult T-cell leukemia, A characte ristic of HTLV-I-transformed T cells is the constitutive nuclear expression of NF-kappa B/Rel family of transcription factors, which appears to be ess ential for the growth of these transformed cells. Although NF-kappa B/Rel f actors are known to induce the expression of T-cell growth factor interleuk in (IL)-2, it is unclear how they participate in the IL-2-independent growt h of HTLV-1-transformed cells, In this study, we show that certain NF-kappa B/Rel members, predominantly c-Rel, interact with enhancer sequences for S TAT5, a key transcription factor mediating IL-2-induced T-cell proliferatio n. Reporter gene assays reveal that the binding of c-Rel to the STAT5 site present in the Fc gamma 1 gene leads to potent transactivation of this enha ncer. Binding of c-Rel to the Fc gamma R1 STAT site also occurs in human pe ripheral blood T cells immortalized with HTLV-I in vitro and is correlated with enhanced levels of proliferation of these cells. These results raise t he possibility that NF-kappa B/Rel may participate in the growth control of HTLV-I-transformed T cells by regulating genes driven by both kappa B and certain STAT enhancers.