Subregions of the Adenovirus E1A Transactivation Domain Target Multiple Components of the TFIID Complex

Abstract

Transcriptional activation by the adenovirus E1A 289R protein requires direct contacts with the TATA box-binding protein (TBP) and also displays a critical requirement for TBP-associated factors (TAFs) (T.G. Boyer and A. J. Berk, Genes Dev. 7:1810-1823, 1993; J. V. Geisberg, W. S. Lee, A. J. Berk, and R. P. Ricciardi, Proc. Natl. Acad. Sci. USA 91:2488-2492, 1994; W. S. Lee, C. C. Kao, G. O. Bryant, X. Liu, and A. J. Berk, Cell 67:365-376, 1991; and Q. Zhou, P. M. Lieberman, T. G. Boyer, and A. J. Berk, Genes Dev. 6:1964-1974, 1992). In this report, we demonstrate that the activation domain of E1A (CR3) specifically binds to two TAFs, human TAFII250 (hTAFII250) and Drosophila TAFII110 (dTAFII110). These interactions can take place both in vivo and in vitro and require the carboxy-terminal region of CR3; the zinc finger region of CR3, which binds TBP, is not needed to bind these TAFs. We mapped the E1A-binding sites on hTAFII250 to an internal region that contains a number of structural motifs, including an HMG box, a bromodomain, and direct repeats. This represents the first demonstration that hTAFII250 may serve as a target of a transcriptional activator. We also mapped the E1A binding on dTAFII110 to its C-terminal region. This is of significance since, by contrast, Sp1-mediated activation requires binding to the N-terminal domain of dTAFII110. Thus, distinct surfaces of dTAFII110 can serve as target sites for different activators. Our results indicate that E1A may activate transcription, in part, through direct contacts of the CR3 subdomains with selected components of the TFIID complex.

Rb interacts with TAFII250/TFIID through multiple domains

“…There appear to be at least two domains in TAF II 250 important for binding the large pocket of Rb (Figure 8). One domain is found within the amino terminus of TAF II 250, whereas the second lies near to or overlaps with the RAP74 (Ruppert and Tijan, 1995) and E1A binding domains (Geisberg et al, 1995). The mapping analysis demonstrates that the large pocket of Rb can bind to both of these domains in TAF II 250, but that the amino terminus of Rb is unable to bind to the amino terminus of TAF II 250.…”

“…In addition to binding TBP and other TAFs, TAF II 250 has also been shown to bind the RAP74 subunit of TFIIF (Ruppert and Tijan, 1995), as well as adenovirus E1A (Geisberg et al, 1995) and HSV-ICP4 (Carrozza and DeLuca, 1996). We have previously demonstrated that Rb can associate with TAF II 250, regulating Sp1-mediated transcription .…”

“…Mapping the domains in TAF II 250 important for binding Rb in vitro TAF II 250 is a large protein able to bind to a number of other TAFs as well as TBP (Chen et al, 1994;Ruppert et al, 1993), RAP74 (Ruppert and Tijan, 1995) and adenovirus E1A (Geisberg et al, 1995). To map the Rb-binding domain(s) in TAF II 250, a series of Nterminal and C-terminal deletions in TAF II 250 were used ( Figure 5a).…”

Adenovirus 5 E1A is responsible for increased expression of insulin receptor substrate 4 in established adenovirus 5-transformed cell lines and interacts with IRS components activating the PI3 kinase/Akt signalling pathway

“…For example, the Rb family of transcriptional corepressors bind to CR1 and CR2, the CBP/p300 family of acetyltransferases bind to the N-terminal region and CR1, whereas CtBP1 and CtBP2 associate with the C-terminal CR4 domain (Whyte et al, 1989;Dyson et al, 1992;Boyd et al, 1993;Eckner et al, 1994;Arany et al, 1995). CR3, exclusive to the E1A13S protein, binds to proteins involved in transcriptional activation, such as TATA binding protein (TBP), Mediator 23 (Med23) and associated transcription factors (ATFs), various transcription factors and proteasome components (Lee et al, 1991;Green, 1990, 1994;Geisberg et al, 1994Geisberg et al, , 1995Boyer et al, 1999;Wang and Berk, 2002;Rasti et al, 2006).…”

The adenovirus E1A binding protein BS69 is a corepressor of transcription through recruitment of N-CoR

“…Deacetylation of histone N-terminal tails can reverse this process and hypoacetylated regions of chromatin are transcriptionally less accessible. E1A interacts with various chromatin modifying proteins, (reviewed by Mymryk and Smith, 1997), some of which display histone acetyltransferase (HAT) activity, such as the transcriptional coactivators CBP/p300 (Ogryzko et al, 1996) and TAF II -250 (Geisberg et al, 1995;Mizzen et al, 1996). Other E1A binding proteins are directly associated with histone deacetylase proteins (HDAc's), like the Rb family of transcriptional repressors (Luo et al, 1998;Brehm et al, 1998;Magnaghi et al, 1998;Ferreira et al, 1998) and the transcriptional regulators YY-1 (Lee et al, 1995;Lewis et al, 1995;Yang et al, 1997) and CtBP (Schaeper et al, 1995;Sundqvist et al, 1998).…”