Association of p300 and CBP with Simian Virus 40 Large T Antigen

Abstract

p300 and the CREB-binding protein CBP are two large nuclear phosphoproteins that are structurally highly related. Both function, in part, as transcriptional adapters and are targeted by the adenovirus E1A oncoprotein. We show here that p300 and CBP interact with another transforming protein, the simian virus 40 large T antigen (T). This interaction depends on the integrity of a region of T which is critical for its transforming and mitogenic properties and includes its LXCXE Rb-binding motif. T interferes with normal p300 and CBP function on at least two different levels. The presence of T alters the phosphorylation states of both proteins and inhibits their transcriptional activities on certain promoters. Although E1A and T show little sequence similarity, they interact with the same domain of p300 and CBP, suggesting that this region exhibits considerable flexibility in accommodating diverse protein ligands.

G1/S transcriptional networks modulated by the HOX11/TLX1 oncogene of T-cell acute lymphoblastic leukemia

“…Considered together with previous data (Kawabe et al, 1997;Shen et al, 2001), perhaps what is most notable about the current findings is that the oncogenic action of HOX11 is remarkably analogous to that of transforming viral proteins. For example, SV40 large T antigen and adenovirus E1A oncoprotein form complexes with Rb and CBP/p300 (Eckner et al, 1996;Ait-Si-Ali et al, 1998), whereas SV40 small t antigen and polyoma virus small and middle T antigens form complexes with PP2A (Pallas et al, 1990;Sontag et al, 1997). In this regard, a critical role for PP2A in human cell transformation has recently come to light .…”

Adenovirus E1A requires the yeast SAGA histone acetyltransferase complex and associates with SAGA components Gcn5 and Tra1

“…This modi®cation alters Tat function in stimulating transcription from viral long terminal repeats (Benkirane et al, 1998;Kiernan et al, 1999;Marzio et al, 1998). Other viral factors such as SV40 T-antigen, papilloma E6, HTLV Tax and KSHV vIRF have been shown to interact with cellular HAT activities (Bex et al, 1998;Eckner et al, 1996;Jayachandra et al, 1999;Patel et al, 1999;Zimmermann et al, 1999). In some cases a clear requirement for HAT activity has been demonstrated, but the coactivator functions of p300 or CBP or as yet uncharacterized functions of P/CAF could also be required by these viral activators.…”

Involvement of Co-activator p300 in the Transcriptional Regulation of the HER-2/neu Gene

“…Among these proteins, the SV40 large T antigen (21) and the estrogen receptor (22) were shown to be capable of binding to the p300 protein and repressing the p300-responsive gene. With the finding that p300, a co-activator in gene regulation, is involved in the HER-2/neu regulation, it would be very interesting to see whether these proteins may also repress HER-2/neu through targeting the common co-activators.…”