Interactions between HTLV-I Tax and NF-kappa B/Rel proteins in T cells.
Members of the NF-kappa B/Rel family of transcription factors are involved in the transcriptional regulation of numerous polypeptides important to the immune response and cellular growth. Several genes regulated in part by NF-kappa B/Rel such as interleukin 2, IL-2 receptor alpha, and GM-CSF are trans-activated via an indirect association with the HTLV-I Tax protein in virus-infected and transformed T cells. In this study, we have investigated the interactions between Tax and NF-kappa B/Rel in an attempt to elucidate the mechanism of Tax mediated trans-activation and its role in leukemogenesis. Transfection studies were performed in Jurkat T cells using expression vectors for individual NF-kappa B subunits and the Tax protein as well as an NF-kappa B regulated reporter plasmid. NF-kappa B proteins differentially trans-activated the HIV-1 enhancer-CAT reporter; co-expression of Tax abrogated the inhibitory effect of I kappa B alpha and a trans-dominant negative mutant of p65 (p65 delta), indicating that Tax was a trans-dominant activator of NF-kappa B-regulated genes. Co-immunoprecipitation studies with extracts from transfected cells and NF-kappa B and Tax subunit specific antibodies revealed that Tax did not co-immunoprecipitate with p50/p105, c-Rel, or I kappa B; however, antibody specific to p65 was able to co-immunoprecipitate a 40kDa protein from Tax-transfected cells. Previous studies have demonstrated a physical interaction between Tax protein and p100, indicating that Tax may preferentially associate with specific NF-kappa B proteins.
Lacoste
J
J
Abe Stern Cancer Research Laboratory, Lady Davis Institute for Medical Research, Sir Mortimer B. Davis-Jewish General Hospital, Montréal, Québec, Canada.
Lanoix
J
J
Pepin
N
N
Hiscott
J
J
D002478:Cells, Cultured; D005786:Gene Expression Regulation; D016356:Gene Products, tax / Q000378:metabolism*; D006801:Humans; D016328:NF-kappa B / Q000378:metabolism*; D011233:Precipitin Tests; D011518:Proto-Oncogene Proteins / Q000378:metabolism*; D020569:Proto-Oncogene Proteins c-rel; D013601:T-Lymphocytes / Q000378:metabolism*; D014162:Transfection
D016356:Gene Products, tax; D016328:NF-kappa B; D011518:Proto-Oncogene Proteins; D020569:Proto-Oncogene Proteins c-rel