Adenovirus serotype determines association and localization of the large E1B tumor antigen with cellular tumor antigen p53 in transformed cells.

Zantema, A.; Schrier, Peter I.; Davis-Olivier, A; Laar, Theo van; Vaessen, R.T.M.J.; Eb, A. J. Van Der

doi:10.1128/mcb.5.11.3084

Cited by 127 publications

(127 citation statements)

References 33 publications

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“…In the AdBRK cells used for this study, WT1 exclusively localizes to the nucleus (data not shown), probably due to the fact that these cells were transformed with the E1A region of adenovirus type 5 and the E1B region of adenovirus type 12. The large E1B protein of adenovirus type 12 appears not to bind to p53 (Zantema et al, 1985). These results all indicate that the eects of WT1 are modulated by other factors in addition to a possible eect of p53.…”

Section: Discussionmentioning

confidence: 49%

EGR-1 enhances tumor growth and modulates the effect of the Wilms' tumor 1 gene products on tumorigenicity

et al. 2000

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The Wilms' tumor 1 gene (WT1) encodes a transcription factor of the zinc-®nger family and is homozygously mutated or deleted in a subset of Wilms' tumors. Through alternative mRNA splicing, the gene is expressed as four main polypeptides that dier by a stretch of 17 amino acids just N-terminal of the four zinc-®ngers and three amino acids between zinc ®ngers 3 and 4. We have previously shown that expression of the WT1(7/7) isoform, lacking both inserts, increases the tumor growth rate of the adenovirus-transformed baby rat kidney (AdBRK) cell line 7C3H2, whereas expression of the WT1(7/+) isoform, lacking the 17aa insert, strongly suppresses the tumorigenic phenotype. In the present study we show that expression of these splice variants does not aect the tumorigenic potential of the similar AdBRK cell line, 7C1T1. In contrast to the 7C3H2 cell line, this AdBRK cell line expresses high endogenous levels of EGR-1 (early growth response-1) protein, a transcription factor structurally related to WT1. Ectopic expression of EGR-1 in the 7C3H2 AdBRK cells signi®cantly increases their in vivo growth rate and nulli®es the tumor suppressor activity of the WT1(7/+) protein. Furthermore, we ®nd that EGR-1 levels are elevated in some Wilms' tumors. These data are the ®rst to show that EGR-1 overexpression causes enhanced tumor growth and that WT1 and EGR-1 exert antagonizing eects on growth regulation in baby rat kidney cells, which might re¯ect the situation in some Wilms' tumors. Oncogene (2000) 19, 791 ± 800.

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Section: Discussionmentioning

confidence: 49%

EGR-1 enhances tumor growth and modulates the effect of the Wilms' tumor 1 gene products on tumorigenicity

et al. 2000

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“…This apparent sequestration within a single cytoplasmic structure is a striking feature of the physical association between E1B 55K and host cell proteins, providing a dramatic illustration of the ability of a viral oncoprotein to inactivate a tumor suppressor gene product (Zantema et al, 1985a). Formation of this cellular structure has been observed with adenovirus serotype 5, whose E1B 55K protein binds p53, but not with serotype 12, whose corresponding E1B 54K protein fails to interact directly with p53 (Zantema et al, 1985b;van den Heuvel et al, 1993). The mechanism underlying formation of the cytoplasmic body and its exact composition are uncertain.…”

Section: Discussionmentioning

confidence: 99%

E1B 55K sequesters WT1 along with p53 within a cytoplasmic body in adenovirus-transformed kidney cells

et al. 1998

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WT1 encodes a tumor suppressor that is expressed in cells of the developing kidney and is inactivated in Wilms tumor, a pediatric kidney cancer. The adenovirus E1B 55K gene product contributes to the transformation of primary baby rat kidney (BRK) cells by binding and inactivating the product of the p53 tumor suppressor. We have previously demonstrated that WT1 and p53 are present within a protein complex in vivo. We now show that WT1 is physically associated with E1B 55K in adenovirus-transformed cells, an interaction that is mediated by the ®rst two zinc ®ngers of WT1. Immunodepletion of p53 abrogates the coimmunoprecipitation of E1B 55K and WT1, consistent with the presence of a trimeric protein complex containing these three proteins. In the presence of E1B 55K, WT1 which is normally localized in the nucleus, is retained within a very high molecular weight complex and sequestered in the characteristic perinuclear cytoplasmic body that contains E1B 55K and p53. Expression of E1B 55K in osteosarcoma cells that undergo apoptosis following expression of WT1 inhibits WT1-mediated cell death. We conclude that E1B 55K may target WT1 along with p53, resulting in the functional inactivation of both tumor suppressor gene products by this viral oncoprotein.

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“…Whilst Ad E1B 54K and 58K proteins share the ability to neutralize p53 there are a number of striking di erences between them. The Ad2/5 proteins bind p53 strongly (Sarnow et al, 1982;Zantema et al, 1985a) with the p53/Ad E1B complex being localized to cytoplasmic dense bodies in Ad2/5 E1-transformed cells (Zantema et al, 1985b;Blair-Zejdal and Blair, 1988). In contrast, Ad12 E1B 54K interacts with p53 only weakly (Grand et al, 1994).…”

Section: Introductionmentioning

confidence: 99%

Consequences of disruption of the interaction between p53 and the larger adenovirus early region 1B protein in adenovirus E1 transformed human cells

et al. 2000

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The adenovirus early region 1B (Ad E1B) genes have no transforming capability of their own but markedly increase the transformation frequency of Ad E1A following co-transfection into mammalian cells. The larger E1B proteins of both Ad2/5 and Ad12 bind to p53 and inhibit its ability to transcriptionally activate other genes. We have previously demonstrated that synthetic peptides identical to the binding sites for p53 on both the Ad2 and Ad12 E1B proteins will disrupt the interaction in vivo and in vitro. In the work presented here we have examined the e ects of complex dissociation on Ad E1-transformed human cells. It has been shown, using confocal microscopy, that when the peptide identical to the p53 binding site was added to Ad5 E1-transformed cells it initally located in the cytoplasmic dense bodies where it caused disruption of the p53/E1B complex. Peptide and p53 then translocated to the nucleus. In Ad12 E1-transformed cells the peptide localized in the nucleus directly and there caused a reorganization of p53 staining from a highly organized,¯e cked' distribution to one in which nuclear staining was homogeneous and di use. Peptides added to either Ad5 E1 or Ad12 E1 transformed cells resulted in the release of transcriptionally active p53. Interestingly, the level of p53 then fell presumably as a result of proteasomal action -this was probably a re¯ection of the short halflife of`free' (i.e. dissociated) p53 compared to that of the bound protein. Free p53 did not cause apoptosis in target cells probably due to the presence of the smaller (19K) E1B proteins. However, addition of peptide leads to a signi®cant reduction in cell growth rate. We have further demonstrated that a signi®cant proportion of those cells which had taken up peptide had ceased DNA synthesis, probably due to a p53-induced cell cycle arrest. The role of the larger E1B protein during transformation is considered in view of these data. Oncogene (2000) 19, 452 ± 462.

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Adenovirus serotype determines association and localization of the large E1B tumor antigen with cellular tumor antigen p53 in transformed cells.

Cited by 127 publications

References 33 publications

EGR-1 enhances tumor growth and modulates the effect of the Wilms' tumor 1 gene products on tumorigenicity

EGR-1 enhances tumor growth and modulates the effect of the Wilms' tumor 1 gene products on tumorigenicity

E1B 55K sequesters WT1 along with p53 within a cytoplasmic body in adenovirus-transformed kidney cells

Consequences of disruption of the interaction between p53 and the larger adenovirus early region 1B protein in adenovirus E1 transformed human cells

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