Role of the E1A Rb-binding domain in repression of the NF-κB-dependent defense against tumor necrosis factor-α

Cook, James L.; Walker, Thomas A.; Worthen, G. Scott; Radke, Jay R.

doi:10.1073/pnas.162082999

Cited by 40 publications

(43 citation statements)

References 73 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…44,45 In addition, adenoviral E1A sensitizes mammalian cells to TNF-α, in part by repressing NF-κB-dependent transcription by altering the function of p65/RelA at a stage after the formation of the transcription factor-enhancer complex. 46 The above hypotheses are being directly tested by our ongoing studies.…”

Section: Discussionmentioning

confidence: 96%

Adenovirus E1A reverses the resistance of normal primary human lung fibroblast cells to TRAIL through DR5 upregulation and caspase 8-dependent pathway

Zhu¹,

Hu²,

Ling³

et al. 2006

Cancer Biology & Therapy

View full text Add to dashboard Cite

Expression of the adenovirus serotype 5 (Ad5) E1A enhances tumor cells to apoptosis by TNF-α, Fas-ligand and TNF-related apoptosis-inducing ligand (TRAIL). In this study, we found that E1A expression reversed the resistance of normal primary human lung fibroblast cells (P-HLF) to TRAIL-induced apoptosis. Furthermore, TRAIL dramatically induced apoptosis of P-HLF cells that expressed E1A following either infection with Ad-E1A or transfection with pcDNA3-E1A. Further results demonstrated that E1A specifically upregulated DR5 levels but had nearly no effect on the levels of DR4. E1A dramatically upregulated the exogenous TRAIL, and then increased a substantial amount of TRAIL on the surface of P-HLF cells treated with the expression vectors, both Ad-TRAIL and pIRES-EGFP-TRAIL. The dominant negative FADD mutation (FADD-DN) results revealed that the apoptosis in Ad-E1A and Ad-TRAIL coinfected P-HLF cells was completely blocked following inhibition of the death receptors-associated apoptosis-inducing molecules FADD. Moreover, the caspase 8 inhibitor (Z-IETD-FMK) could efficiently block caspase 8 activation and resulted in inhibition of caspase 3 activation and cleavage. However, The caspase 9 specific inhibitor (Z-LEHD-FMK) could not counteract the synergistic effect of TRAIL-induced apoptosis in combination with E1A, and caspase 3 activation and cleavage were not inhibited by Z-LEHD-FMK. Thus, our results suggest that adenovirus E1A sensitizes P-HLF cells to TRAILinduced apoptosis involving DR5 upregulation and the caspase 8-dependent pathway. These findings provide the first direct evidence for molecular mechanisms of adenovirus E1A gene products to sensitize normal cells to TRAIL-mediated apoptosis.

show abstract

Section: Discussionmentioning

confidence: 96%

Adenovirus E1A reverses the resistance of normal primary human lung fibroblast cells to TRAIL through DR5 upregulation and caspase 8-dependent pathway

Zhu¹,

Hu²,

Ling³

et al. 2006

Cancer Biology & Therapy

View full text Add to dashboard Cite

show abstract

“…Transcriptional repression by E1A has been demonstrated for a variety of genes induced by transcription factors such as AP1, STAT, C/EBP␤, and NF-B (21,58). This correlates with the ability of E1A to bind and sequester the transcriptional coactivators p300/CBP and components of the recently described transformation-transactivation domain-associated protein (TRRAP) complexes (51).…”

Section: Discussionmentioning

confidence: 97%

“…Although E1A is responsible for the increased tumor necrosis factor alpha sensitivity (4), E1A also counteracts this induction by interfering with the transcriptional activity of NF-B (21).…”

mentioning

confidence: 99%

Strategic Attack on Host Cell Gene Expression during Adenovirus Infection

Zhao¹,

Granberg²,

Elfineh³

et al. 2003

J Virol

View full text Add to dashboard Cite

To understand the interaction between the virus and its host, we used three sources of cDNA microarrays to examine the expression of 12,309 unique genes at 6 h postinfection of HeLa cells with high multiplicities of adenovirus type 2. Seventy-six genes with significantly changed expression ratios were identified, suggesting that adenovirus only modulates expression of a limited set of cellular genes. Quantitative real-time PCR analyses on selected genes were performed to confirm the microarray results. Significantly, a pronounced transcriptional activation by the promiscuous E1A-289R transcriptional activator was not apparent. Instead, promoter sequences in 45% of the upregulated genes harbored a potential E2F binding site, suggesting that the ability of the amino-terminal domain of E1A to regulate E2F-dependent transcription may be a major pathway for regulation of cellular gene expression. CDC25A was the only upregulated gene directly involved in cell cycle control. In contrast, several genes implicated in cell growth arrest were repressed. The transforming growth factor beta superfamily was specifically affected in the expression of both the upstream ligand and an intracellular regulator. In agreement with previous reports, adenovirus also targeted the innate immune response by downregulating several cytokines, including CLL2, CXCL1, and interleukin-6. Finally, stress response genes encoding GADD45B, ATF3, and TP53AP1 were upregulated. Importantly, we also found a novel countermeasure-activation of the apoptosis inhibitor survivin.

show abstract

“…Thus, many viruses have evolved distinct strategies to attenuate NF-B activation. Known mechanisms of NF-B suppression in virus-infected cells include (1) inhibition of the IKK activity and IB phosphorylation, 25 (2) inhibition of the NF-B nuclear translocation, 26 (3) induction of the caspasemediated cleavage of the RelA subunit, 27 and (4) inhibition of NF-B RelA transcriptional activation through protein-protein interaction. 28 Although NF-B activation by Tax has been reported, it remains unknown whether other viral proteins act on the NF-B pathway.…”

Section: Introductionmentioning

confidence: 99%

Human T-cell leukemia virus type 1 bZIP factor selectively suppresses the classical pathway of NF-κB

Zhao

Yasunaga

Satou

et al. 2009

Blood

158

186

View full text Add to dashboard Cite

Role of the E1A Rb-binding domain in repression of the NF-κB-dependent defense against tumor necrosis factor-α

Cited by 40 publications

References 73 publications

Adenovirus E1A reverses the resistance of normal primary human lung fibroblast cells to TRAIL through DR5 upregulation and caspase 8-dependent pathway

Adenovirus E1A reverses the resistance of normal primary human lung fibroblast cells to TRAIL through DR5 upregulation and caspase 8-dependent pathway

Strategic Attack on Host Cell Gene Expression during Adenovirus Infection

Human T-cell leukemia virus type 1 bZIP factor selectively suppresses the classical pathway of NF-κB

Contact Info

Product

Resources

About