Functional domains of adenovirus type 5 E1a proteins

Lillie, James W.; Loewenstein, Paul M.; Green, Michael R.; Green, Maurice

doi:10.1016/0092-8674(87)90175-9

Cited by 281 publications

(218 citation statements)

References 44 publications

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“…Importantly, of the transactivation pathways through which E1A acts, that involving CR3 is the most potent, and most of the activation of viral early genes and of exogenous cellular genes by E1A is brought about by this region (Shenk and Flint, 1991). This region alone is sufficient to activate transcription (Lillie et al, 1987). Relevant to our study, this region is intact in the CB1 construct.…”

Section: Discussionsupporting

confidence: 54%

A novel E1A–E1B mutant adenovirus induces glioma regression in vivo

et al. 2004

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Malignant gliomas are the most frequently occurring primary brain tumors and are resistant to conventional therapy. Conditionally replicating adenoviruses are a novel strategy in glioma treatment. Clinical trials using E1B mutant adenoviruses have been reported recently and E1A mutant replication-competent adenoviruses are in advanced preclinical testing. Here we constructed a novel replication-selective adenovirus (CB1) incorporating a double deletion of a 24 bp Rb-binding region in the E1a gene, and a 903 bp deleted region in the E1b gene that abrogates the expression of a p53-binding E1B-55 kDa protein. CB1 exerted a potent anticancer effect in vitro in U-251 MG, U-373 MG, and D-54 MG human glioma cell lines, as assessed by qualitative and quantitative viability assays. Replication analyses demonstrated that CB1 replicates in vitro in human glioma cells. Importantly, CB1 acquired a highly attenuated replicative phenotype in both serum-starved and proliferating normal human astrocytes. In vivo experiments using intracranially implanted D-54 MG glioma xenografts in nude mice showed that a single dose of CB1 (1.5 Â 10 8 PFU/tumor) significantly improved survival. Immunohistochemical analyses of expressed adenoviral proteins confirmed adenoviral replication within the tumors. The CB1 oncolytic adenovirus induces a potent antiglioma effect and could ultimately demonstrate clinical relevance and therapeutic utility.

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Section: Discussionsupporting

confidence: 54%

A novel E1A–E1B mutant adenovirus induces glioma regression in vivo

et al. 2004

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“…Another cellular E1A binding protein, termed p400, whose E1A contact overlaps residues 12 ± 35 (Barbeau et al, 1994;Lillie et al, 1987), and thus the TRRAP binding region, has recently been identi®ed. The p400 protein is related to SWI2/SNF2 and forms a complex with TRRAP and other proteins (Fuchs et al, 2001).…”

Section: Discussionmentioning

confidence: 99%

Recruitment of TRRAP required for oncogenic transformation by E1A

et al. 2001

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TRRAP links Myc with histone acetylases and appears to be an important mediator of its oncogenic function. Here we show that interaction with TRRAP is required for cellular transformation not only by Myc, but also by the adenovirus E1A protein. Substitution of the 262 Nterminal residues of Myc with a small domain of E1A (residues 12 ± 54) restores Myc transforming function. E1A(12 ± 54) contains a TRRAP-interaction domain, that recruits TRRAP to either E1A ± Myc chimeras, or the native 12S E1A protein. Overexpression of a competing TRRAP fragment in vivo blocks interaction of cellular TRRAP with either E1A ± Myc or E1A, and suppresses cellular transformation by both oncoproteins. Moreover, E1A(D26 ± 35) that fails to bind TRRAP but is capable of binding the Retinoblastoma (Rb)-family and p300/CBP proteins is defective in cellular immortalization, transformation and cell cycle deregulation. Thus in addition to disrupting Rb and p300/CBP functions, E1A must recruit TRRAP to transform cells. Oncogene (2001) 20, 8270 ± 8275.

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“…The E1A proteins of various serotypes share three conserved regions. Conserved region 1 and 2 are largely responsible for the cell cycle stimulatory activity (Lillie et al, 1987;Whyte et al, 1989). 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).…”

Section: Introductionmentioning

confidence: 99%

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

Masselink

Bernards

2000

Oncogene

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BS69 was ®rst identi®ed as a protein that interacts directly with the transactivation domain (conserved region 3) of the 289R adenovirus type 5 E1A protein.We show here that BS69 is a potent repressor of transcription. BS69 mediates repression, at least in part, through interaction with the co-repressor N-CoR. BS69 interacts with N-CoR through a MYND domain in its carboxyl terminus. A recently cloned splice variant of BS69, designated BRAM1, is also capable of interacting with N-CoR and E1A, but unlike BS69, is not able to repress transcription, indicating that N-CoR interaction is necessary but not su cient for BS69 repression. Expression of E1A inhibits repression mediated by BS69. Our data suggest that BS69 participates in transcriptional repressor complexes and that E1A can modulate these complexes through interaction with BS69. Oncogene (2000) 19, 1538 ± 1546.

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Functional domains of adenovirus type 5 E1a proteins

Cited by 281 publications

References 44 publications

A novel E1A–E1B mutant adenovirus induces glioma regression in vivo

A novel E1A–E1B mutant adenovirus induces glioma regression in vivo

Recruitment of TRRAP required for oncogenic transformation by E1A

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

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