Mutant p53 Forms a Complex with Sp1 on HIV-LTR DNA

Author: Chicas A.   Molina P.   Bargonetti J.  

Publisher: Elsevier

ISSN: 0006-291X

Source: Biochemical and Biophysical Research Communications, Vol.279, Iss.2, 2000-12, pp. : 383-390

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Abstract

Many mutants of p53 activate HIV-LTR driven transcription and promote HIV replication. The region of the HIV-LTR containing Sp1-binding sites is important for this effect. In this study we test the hypothesis that mutant p53 interacts with DNA-bound Sp1 and in this way can increase transcription from Sp1-dependent promoters. We have used the breast cancer cell line MDA-MB-468 that expresses endogenous mutant p53His273 as our source of p53 protein. First, we demonstrated that this mutant p53 participates in activating transcription from the HIV-LTR by showing that HIV-LTR-directed transcription in MDA-MB-468 cells is inhibited in a dominant-negative manner by p53Val135. Using HIV-LTR DNA affinity chromatography, we detected coelution of p53His273 and Sp1. We also demonstrated that this mutant p53 binds sequence specifically to the super consensus sequence (SCS) and that Sp1 coeluted with p53His273 from a column containing this site. These data indicate that p53His273 can associate with DNA-bound Sp1 suggesting that activated HIV-LTR transcription associated with mutant p53 occurs through a DNA driven multi-protein complex.

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