A cofactor, TIP30, specifically enhances HIV-1 Tatactivated transcription

Abstract

Replication of HIV-1 requires the viral Tat protein, which increases the extent of transcription elongation by RNA polymerase II after activation at the single viral long terminal repeat (LTR) promoter. This effect of Tat on transcription requires Tat interactions with a 5 region (TAR) in nascent transcripts as well as Tat-specific cofactors. The present study identifies a cellular protein, TIP30, that interacts with Tat and with an SRB-containing RNA polymerase II complex both in vivo and in vitro. Coexpression of TIP30 specifically enhances transactivation by Tat in transfected cells, and immunodepletion of TIP30 from nuclear extracts abolishes Tat-activated transcription without affecting Tatindependent transcription. These results implicate TIP30 as a specific coactivator that may enhance formation of a Tat-RNA polymerase II holoenzyme complex.

The Transcriptome of Prematurely Aging Yeast Cells Is Similar to That of Telomerase-deficient Cells

“…As with other genes in the environmental stress response, the number of these genes induced and the extent of change varies with the type of damaging agent and the dose (Gasch et al, 2001;Gasch and Werner-Washburne, 2002). Among the DNA "signature" genes are RAD51 and RAD54, genes involved in homologous recombination; DUN1, involved in the Mec1-mediated DNA damage checkpoint response; RNR2 and RNR4, affecting ribonucleotide reductase subunits; PLM2, which has homology to the forkhead-associated domain found in a number of transcription factors and kinases; DIN7, encoding a damage inducible mitochondrial protein with homologies to nucleases; YER004w, which has homology to the human protein Tip30, a tumor repressor that mediates apoptosis (Shtivelman, 1997;Xiao et al, 1998); and YBR070c, of unknown function. We find that in old wild-type cells RAD51, RAD54, DUN1, and YBR070c are induced (Figure 8).…”

TIP30 Directly Binds p53 Tumor Suppressor Protein In Vitro

“…This hypothesis could be tested by investigating the effects of TIP30 on the in vitro transcriptional activity of p53. Such a cofactor function of TIP30 has previously been reported in relation to Tat protein regulation of HIV-1 mRNA transcription (Xiao et al, 1998). Second, TIP30 may act as a regulator of importin activity.…”

“…In the following year human TIP30 was shown to specifically enhance human immunodeficiency virus-1 (HIV-1) Tatactivated transcription (Xiao et al, 1998). The amino acid sequence of human TIP30 was later confirmed to be identical to that of human CC3 (Xiao et al, 1998).…”

“…In the following year human TIP30 was shown to specifically enhance human immunodeficiency virus-1 (HIV-1) Tatactivated transcription (Xiao et al, 1998). The amino acid sequence of human TIP30 was later confirmed to be identical to that of human CC3 (Xiao et al, 1998). TIP30, which exhibits decreased expression in some cancer cells NicAmhlaoibh and Shtivelman, 2001;Shtivelman, 1997;Tong et al, 2009;Zhao et al, 2006), is a tumor suppressor with proapoptotic activity (El Omari et al, 2005;Xiao et al, 2000;Zhao et al, 2007) as well as with anti-metastatic Shtivelman, 1997;Tong et al, 2009;Xiao et al, 2000;Zhao et al, 2007) and angiogenesis-inhibiting (NicAmhlaoibh and Shtivelman, 2001) properties.…”

“…Our results on the direct binding between TIP30 and p53 suggest two possibilities. First, it is possible that TIP30 may act as a cofactor for p53 in the transcriptional regulation of the Bax gene (Xiao et al, 1998), encoding a well-known apoptotic factor. This hypothesis could be tested by investigating the effects of TIP30 on the in vitro transcriptional activity of p53.…”