Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P51532 (transcriptional activator)
 6,546 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Apoptosis is an important regulatory process during normal development and maturation. We find that the proliferation-arresting and differentiation-inducing compound sodium n-butyrate (NaB) triggers a marked host chromatin degradation. This apoptotic process is independent of, but commensurate with, a rapid increase in viral mRNA synthesis and subsequent release of HIV-1 virus in transformed human cell lines harboring tat- (HLM1) or tat+ (U1, ACH-2) dormant HIV-1 proviruses. This compound stimulates a reversible accumulation of the characteristic viral mRNAs at a much faster rate than two other DNA degradation inducers such as tumor necrosis factor-alpha and phorbol 12-myristate 13-acetate. The transcriptional activator butyrate analogue, alpha-amino-n-butyrate, failed to cause similar phenotypic changes. These results suggest that common regulatory signals may be involved in activation of apoptosis genes and latent provirus by NaB.
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PMID:Induction of developmentally programmed cell death and activation of HIV by sodium butyrate. 800 66

The p53 tumor suppressor gene product, a sequence-specific DNA-binding protein, has been shown to act as a transcriptional activator and repressor both in vitro and in vivo. Consistent with its role in regulating transcription are recent observations that the N-terminal acidic domain of p53 binds directly to the TATA box-binding protein subunit of the general transcription factor, TF IID. It is now demonstrated that wild-type p53 (wt-p53) inhibits human immunodeficiency virus type 1 (HIV-1) long terminal repeat (LTR)-directed chloramphenicol acetyltransferase activity in a cotransfection assay system. Importantly, this effect of wt-p53 on the HIV-1 LTR was also demonstrated by in vitro transcription assays. In addition, the Sp1 sites and the TATA box of the HIV-1 LTR are demonstrated to be the primary sites involved with p53-induced effects on this viral promoter. The upstream elements of the HIV-1 LTR, including the nuclear factor kappa B (NF-kappa B) binding sites, decrease the p53-induced inhibitory effects on viral transcription. In the presence of the HIV-1 TAR sequence and Tat protein, the HIV-1 LTR also becomes less sensitive to wt-p53-induced inhibition. By using a retroviral vector delivery system, mutant forms of p53 genes were expressed in two HIV-1 latently infected cell lines, ACH-2 and U1. In the ACH-2 cell line, which is now demonstrated to contain an endogenous mutant form of p53 (amino acid 248, Arg to Gln), additional mutant p53 proteins did not alter HIV-1 replication. In U1 cells, which completely lack endogenous p53, overexpression of mutant p53 led to an increase in HIV-1 replication. Thus, these data indicate a possible functional role for wt-p53 and mutant p53 proteins in the control of HIV-1 replication patterns and proviral latency.
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PMID:The tumor suppressor protein p53 strongly alters human immunodeficiency virus type 1 replication. 820 5