DIFFERENT MEMBERS OF THE SP1 MULTIGENE FAMILY EXERT OPPOSITE TRANSCRIPTIONAL REGULATION OF THE LONG TERMINAL REPEAT OF HIV-1

Recently, a family of transcription factors structurally related to Sp 1 has been described; thus, more than one activator may bind to the GC boxes present in a number of viral and cellular promoters. We have co mpared the transactivation potentials of Sp1, Sp3 and Sp4 proteins on the human immunodeficiency virus type 1 (HIV-1) promoter. The long ter minal repeat (LTR) of HIV-1 contains three binding sites for the trans cription factor Sp1 (GC boxes) which are involved in both basal and Ta t-mediated transcriptional activation. Moreover, a cooperative interac tion between NF-kappa B and Sp1 is required for HIV enhancer activatio n. We now demonstrate that Sp4 is an activator, while the Sp3 protein represses basal expression of HIV promoter. Remarkably, we found that over-expression of the transcription factor Sp3 was able to suppress T at-mediated transactivation. These inhibitory effects of Sp3 correlate with its DNA binding activity, suggesting that Sp3 inhibition involve s competition with Sp1 for occupancy of the GC boxes. Next, we have an alyzed the role of different Sp1-related proteins in the stimulation o f HIV-1 promoter in response to mitogens. We found that the binding of NF-kappa B is not by itself sufficient to induce HIV gene expression. Instead, an interaction between NF-kappa B and the trans-acting domai n (A domain) of Sp1 bound to an adjacent site must occur. We found tha t the cooperative interaction between NF-kappa B and Sp1 is highly spe cific, since neither Sp3 nor Sp4 is capable of cooperating with NF-kap pa B.