Mutual Interference of Adenovirus Infection and
            <i>myc</i>
            Expression

Löhr, Kristina; Hartmann, Oliver; Schäfer, Helmut; Dobbelstein, Matthias

doi:10.1128/jvi.77.14.7936-7944.2003

Cited by 18 publications

(25 citation statements)

References 50 publications

(48 reference statements)

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“…1B). Although Baluchamy et al (7) have reported that adenovirus activates Myc gene expression, these experiments were done in quiescent cells; our assays, and those of Lohr et al (5), were performed in cycling cells, suggesting that regulation of Myc transcription by adenovirus is influenced by the growth status of the cells.…”

Section: Resultsmentioning

confidence: 79%

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Adenovirus E1A targets p400 to induce the cellular oncoprotein Myc

Tworkowski

Chakraborty

Samuelson

et al. 2008

Proc. Natl. Acad. Sci. U.S.A.

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Adenovirus E1A drives oncogenesis by targeting key regulatory pathways that are critical for cellular growth control. The interaction of E1A with p400 is essential for many E1A activities, but the downstream target of this interaction is unknown. Here, we present evidence that the oncoprotein transcription factor Myc is the target of this interaction. We show that E1A stabilizes Myc protein via p400 and promotes the coassociation of Myc and p400 at Myc target genes, leading to their transcriptional induction. We also show that E1A requires Myc for its ability to activate Mycdependent gene expression and induce apoptosis, and that forced expression of Myc is sufficient to rescue the activity of an E1A-mutant defective in p400 binding. Together, these findings establish that Myc, via p400, is an essential downstream target of E1A.proteolysis ͉ transcription ͉ transformation ͉ apoptosis

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Section: Resultsmentioning

confidence: 79%

“…Recently, it was reported that E1A can inhibit the ubiquitin (Ub)-mediated destruction of Myc during the course of adenovirus infection (5). It has also been reported that E1A can interact with multiple subunits of the 19S proteasome to inhibit proteasomal proteolysis (6).…”

mentioning

confidence: 99%

Adenovirus E1A targets p400 to induce the cellular oncoprotein Myc

Tworkowski

Chakraborty

Samuelson

et al. 2008

Proc. Natl. Acad. Sci. U.S.A.

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“…C-myc expression is thought to be a branch point from which the cells either go towards cell-cycle re-entry or commit to terminal differentiation. Lohr et al 18 showed that adenoviral infection directly affects the c-myc expression in HeLa cells. They suggested that adenoviral E1A product alone can increase the stability and maintain a steady state of myc proteins and further concluded that overexpression of myc gene inhibits adenoviral replication 'at a stage after earlygene expression but during the replication of virus DNA.'…”

Section: Choice Of Cellsmentioning

confidence: 99%

Viral mRNA expression but not DNA replication is required for lipogenic effect of human adenovirus Ad-36 in preadipocytes

Rathod

Vangipuram²,

Krishnan

et al. 2006

Int J Obes

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Objective: Human adenovirus Ad-36 causes adiposity in animal models and shows association with human obesity. Ad-36 enhances differentiation of 3T3-L1 and human preadipocytes, without cell lysis, a characteristic that may contribute to its adipogenic effect observed in vivo. Ad-2, another human adenovirus is nonadipogenic in animals and in 3T3-L1 cells and shows no correlation with human obesity. The objective of this study was to determine the adipogenic roles of viral mRNA and DNA, which may explain the differential effects of Ad-36 and Ad-2 on preadipocyte differentiation. Methods: This study determined the duration of selected Ad-36 gene expression in 3T3-L1 cells, and the effect on preadipocytes differentiation, when Ad-36 gene expression was attenuated by Cidofovir, an antiadenoviral agent. Results:The results showed that Ad-36, but not Ad-2, expresses viral mRNA. Ad-36 gene expression peaked at 2-4 days postinoculation and very low levels persisted after day 7. Despite the viral mRNA expression, Ad-36 infection of 3T3-L1 cells was abortive as indicated by a progressive decrease in viral DNA quantity. Attenuation of Ad-36 mRNA expression by Cidofovir reduced the adipogenic effect of the virus. Conclusion: In conclusion, viral mRNA expression, although transient, is a prerequisite for enhancing differentiation of preadipocytes by Ad-36. Viral DNA replication was not required for the effect. This is the first evidence for the role of gene expression of an adipogenic human virus in enhancing preadipocytes differentiation. This study provides the basis for further understanding novel regulatory modulators of preadipocytes differentiation.

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“…Chips were scanned with a GMS 418 fluorescent scanner (MWG-Biotech), and the images were analyzed with IMAGENE 3.0 software. The raw data were evaluated as described previously (18).…”

Section: Methodsmentioning

confidence: 99%

Programmed cell death protein 4 suppresses CDK1/cdc2 via induction of p21^Waf1/Cip1

Göke¹,

Barth²,

Schmidt³

et al. 2004

American Journal of Physiology-Cell Physiology

129

116

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Waf1/Cip1 inhibits CDK4/6 and CDK2. Decrease of CDK4/6 and CDK2 enhances the binding of pRb to E2F/DP, which in turn together bind to and repress the cdc2 promoter. Upregulation of CDK1/cdc2 accompanied by a malignant change was previously reported in colon cancer. We show that expression of pdcd4 as an indirect suppressor of CDK1/cdc2 is lost in progressed carcinomas of lung, breast, colon, and prostate. Furthermore, it seems that localization and expression of pdcd4 directly correlate with tumor progression. Finally, the CDK1/cdc2 inhibitor roscovitine reduces the proliferation of several tumor cell lines, suggesting that inhibition of CDK1/cdc2 may be a useful strategy against malignant transformation. Therefore, pdcd4 might serve as a novel target for antineoplastic therapies. tumor growth; cell cycle; tumor suppressor gene INVESTIGATING THE MECHANISMS of programmed cell death, we cloned rat pdcd4 (ϭDUG, death upregulated gene) (8). Rat pdcd4 is highly conserved during evolution and almost identical to the murine [MA3 (25), TIS (22)] human [H731 (19), 197/15a (2)], and chicken (24) homologs. pdcd4 is upregulated after induction of apoptosis by different stimuli such as glucose/serum starvation and death receptor ligation (for review of pdcd4 see Ref. 15). Although the role of pdcd4 during apoptosis is still unclear, there is increasing evidence that pdcd4 might function as a tumor suppressor (32). Promotion-sensitive (Pϩ) JB6 cells undergo neoplastic transformation in response to tumor promoters. Interestingly, (PϪ) JB6 cells, which are promotion resistant, show higher pdcd4 expression levels of mRNA and protein compared with Pϩ cells (4). Decrease of pdcd4 protein expression by an antisense approach resulted in a transformation-sensitive Pϩ phenotype. In accordance with these findings, higher pdcd4 mRNA levels have been found in preneoplastic and initiated keratinocyte cell lines than in further-progressed cell lines. Most likely, pdcd4 inhibits the transactivation of the transcription factor complex AP-1, which is essential for neoplastic transformation, by controlling an unknown modulator of c-fos and c-jun activation domains (33). This might, at least partially, explain its tumor-suppressive effect. However, there is evidence that pdcd4 also acts via other signaling pathways. Analysis of the amino acid sequence revealed that pdcd4 contains two conserved MA3 domains. The translation initiation factors eukaryotic initiation factor (eIF)4G I and eIF4G II directly interact with the RNA helicase eIF4A via the MA3 domain (23). eIF4A is part of the capdependent translation initiation complex and unwinds the mRNA. Recently, we showed (8) that, similarly to eIF4G, pdcd4 interacts directly with eIF4A. In addition, this was confirmed by Yang et al. (31), who showed that this interaction inhibits protein synthesis. Futhermore, in in vitro binding assays, pdcd4 prevented binding of eIF4A to the carboxyterminal domain of eIF4G. The mechanisms of action of pdcd4 might even be more complex, because it was reported that ...

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Mutual Interference of Adenovirus Infection and myc Expression

Cited by 18 publications

References 50 publications

Adenovirus E1A targets p400 to induce the cellular oncoprotein Myc

Adenovirus E1A targets p400 to induce the cellular oncoprotein Myc

Viral mRNA expression but not DNA replication is required for lipogenic effect of human adenovirus Ad-36 in preadipocytes

Programmed cell death protein 4 suppresses CDK1/cdc2 via induction of p21^Waf1/Cip1

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Mutual Interference of Adenovirus Infection and myc Expression

Cited by 18 publications

References 50 publications

Adenovirus E1A targets p400 to induce the cellular oncoprotein Myc

Adenovirus E1A targets p400 to induce the cellular oncoprotein Myc

Viral mRNA expression but not DNA replication is required for lipogenic effect of human adenovirus Ad-36 in preadipocytes

Programmed cell death protein 4 suppresses CDK1/cdc2 via induction of p21Waf1/Cip1

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Programmed cell death protein 4 suppresses CDK1/cdc2 via induction of p21^Waf1/Cip1