Molecular cloning and functional analysis of the adenovirus E1A-associated 300-kD protein (p300) reveals a protein with properties of a transcriptional adaptor.

Abstract

The growth-controlling functions of the adenovirus E1A oncoprotein depend on its ability to interact with a set of cellular proteins. Among these are the retinoblastoma protein, p107, p130, and p300. We have isolated a cDNA encoding full-length human p300 and mapped the chromosomal location of the gene to chromosome 22q13. p300 contains three cysteine-and histidine-rich regions of which the most carboxy-terminal region interacts specifically with E1A. In its center, p300 contains a bromodomain, a hallmark of certain transcriptional coactivators. We have examined the ability of p300 to overcome the repressive effect of E1A on the SV40 enhancer. We show that p300 molecules lacking an intact E1A-binding site can bypass E1A repression and restore to a significant extent the activity of the SV40 enhancer, even in the presence of high levels of E1A protein. These results imply that p300 may function as a transcriptional adaptor protein for certain complex transcriptional regulatory elements.[Key Words: p300; transcriptional adaptor protein; E 1 A-binding protein; cell cycle regulatory protein]

Detection of CBP rearrangements in acute myelogenous leukemia with t(8;16)

“…Interestingly, CBP exhibits extensive homology to the E1A-associated protein p300, and the two proteins appear to be functionally homologous. 46 This molecular redundancy, coupled with the genomic location of p300 on chromosome band 22q13, 47 leads us to speculate that the t(8;22) is in fact a fusion involving p300 and MOZ.…”

p300 is required for orderly G1/S transition in human cancer cells

“…The transcriptional coactivators p300 and CBP are highly conserved paralogous proteins, first identified by their interactions with adenoviral E1A and CREB (cAMP response element binding protein) respectively (Chrivia et al, 1993;Eckner et al, 1994). p300/CBP regulate gene expression through interactions with nuclear proteins and participate in a broad spectrum of biological activities, including cell cycle regulation, differentiation, apoptosis and the DNA damage response (Giordano and Avantaggiati, 1999;Goodman and Smolik, 2000).…”

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

“…Conserved region 3 is unique to the larger 13S form of E1A and encodes a domain that exhibits strong transactivation potential (Green et al, 1988) and interacts with the mammalian Srb/Mediator complex (Boyer et al, 1999). The transforming activity of E1A, residing mainly in the conserved regions 1 and 2 (Whyte et al, 1998b), is brought about by interaction with a large number of cellular proteins, many of which are cell cycle regulatory proteins involved in transcription and/or chromatin modi®cation such as Rb (Whyte et al, 1998a), p107 and p130 (Whyte et al, 1989;Hannon et al, 1993), cyclins A and E (Pines and Hunter, 1990;Giordano et al, 1991), the cdk inhibitor p27 kip1 (Mal et al, 1996) and the transcriptional adaptors p300 and CBP (Arany et al, 1994;Eckner et al, 1994).…”