Adenovirus E1B 55-Kilodalton Oncoprotein Inhibits p53 Acetylation by PCAF

Liu, Yue; Colosimo, April; Yang, Xiang-Jiao; Liao, Daiqing

doi:10.1128/mcb.20.15.5540-5553.2000

Cited by 88 publications

(77 citation statements)

References 71 publications

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“…Both NS3 and NS5 viral proteins, when being overexpressed in cells, cause the downregulation of p53-dependent transactivational activity. It is known that the extreme C-terminal domain of p53 interacts with numerous viral proteins, cellular transcription factors, and a wide range of cellular kinases, including HBV X protein (Truant et al, 1995), adenovirus E4orf6 (Dobner et al, 1996), TBP (Martin et al, 1993), TFIIH (Xiao et al, 1994), PCAF (Liu et al, 2000), and CKII (Filhol et al, 1992). Through the physical interactions with these protein factors, the functional status of p53 is finely regulated.…”

Section: Discussionmentioning

confidence: 99%

Modulation of p53 transcription regulatory activity and post-translational modification by hepatitis C virus core protein

Kao

Chen

Chen³

et al. 2004

Oncogene

115

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Oncogenic virus proteins often target to tumor suppressor p53 during virus life cycle. In the case of hepatitis C virus (HCV) core protein, it has been shown to affect p53-dependent transcription. Here, we further characterized the in vitro and in vivo interactions between HCV core protein and p53 and showed that these two proteins colocalized in subnuclear granular structures and the perinuclear area. By use of a reporter assay, we observed that while low level of HCV core protein enhanced the transactivational activity of p53, high level of HCV core protein inhibited this activity. In both cases, however, HCV core protein increased the p53 DNA-binding affinity in gel retardation analyses, likely due to the hyperacetylation of p53 Lys 373 and Lys 382 residues. Additionally, HCV core protein, depending on its expression level, had differential effects on the Ser 15 phosphorylation of p53. Moreover, HCV core protein could rescue p53-mediated suppressive effects on both RNA polymerase I and III transcriptions. Collectively, our results indicate that HCV core protein targets to p53 pathway via at least three means: physical interaction, modulation of p53 gene regulatory activity and post-translational modification. This feature of HCV core protein, may potentially contribute to the HCV-associated pathogenesis.

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Section: Discussionmentioning

confidence: 99%

Modulation of p53 transcription regulatory activity and post-translational modification by hepatitis C virus core protein

Kao

Chen

Chen³

et al. 2004

Oncogene

115

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“…All NLS are rich in lysine residues. It is known that lysine K320 in Hsp53 NLS I, which is highly conserved between species, is acetylated to enhance p53 stability and p53-specific DNA binding with p53-regulated proteins (Liu et al, 2000). Nuclear import of p53 is enabled by its NLS while nuclear export is enabled by its nuclear export signal (NES) which is located within the tetramerization domain (see below).…”

Section: Mytilus P53 Dna Binding Domainsmentioning

confidence: 99%

Identification and phylogenetic comparison of p53 in two distinct mussel species (Mytilus)

Muttray

Cox

St-Jean

et al. 2005

Comparative Biochemistry and Physiology Part C: Toxicology &

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The extent to which humans and wildlife are exposed to anthropogenic challenges is an important focus of environmental research. Potential use of p53 gene family marker(s) for aquatic environmental effects monitoring is the long-term goal of this research. The p53 gene is a tumor suppressor gene that is fundamental in cell cycle control and apoptosis. It is mutated or differentially expressed in about 50 % of all human cancers and p53 family members are differentially expressed in leukemic clams. Here we report the identification and characterization of the p53 gene in two species of Mytilus, Mytilus edulis and Mytilus trossulus, using RT-PCR with degenerate and specific primers to conserved regions of the gene. The Mytilus p53 proteins are 99.8 % identical and closely related to clam (Mya) p53. In particular, the 3' untranslated regions were examined to gain understanding of potential post-transcriptional regulatory pathways of p53 expression. We found nuclear and cytoplasmic polyadenylation elements, adenylate/uridylate-rich elements, and a K-box motif previously identified in other, unrelated genes. We also identified a new motif in the p53 3'UTR which is highly conserved across vertebrate and invertebrate species. Differences between the p53 genes of the two Mytilus species may be part of genetic determinants underlying variation in leukemia prevalence and/or development, but this requires further investigation. In conclusion, the conserved regions in these p53 paralogues may represent potential control points in gene expression. This information provides a critical first step in the evaluation of p53 expression as a potential marker for environmental assessment.

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“…Similarly, various WT and mutant p53 constructs were fused with Gal4 TAD. Yeast two-hybrid assays were conducted as described (25).…”

Section: Methodsmentioning

confidence: 99%

Negative Regulation of p53 Functions by Daxx and the Involvement of MDM2

Zhao

Liu

Sidhu

et al. 2004

Journal of Biological Chemistry

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In normal cells p53 activity is tightly controlled and MDM2 is a known negative regulator. Here we show that via its acidic domain, Daxx binds to the COOH-terminal domain of p53, whose positive charges are critical for this interaction, as Lys to Arg mutations preserved, but Lys to Ala or Ser to Glu mutations abolished Daxx-p53 interaction. These results thus implicate acetylation and phosphorylation of p53 in regulating its binding to Daxx. Interestingly, whereas Daxx did not bind to p53 in cells as assessed by immunoprecipitation, MDM2 expression restored p53-Daxx interaction, and this correlated with deacetylation of p53. In p53/MDM2-null mouse embryonic fibroblasts (DKO MEF), Daxx repressed p53 target promoters whose p53-binding elements were required for the repression. Coexpression of Daxx and MDM2 led to further repression. p53 expression in DKO MEF induced apoptosis and Daxx expression relieved this effect. Similarly, in HCT116 cells, Daxx conferred striking resistance to 5-fluorouracil-induced apoptosis. As p53 is required for 5-fluorouracil-induced cell death, our data show that Daxx can suppress cell death induced by p53 overexpression and p53-dependent stress response. Collectively, our data reveal Daxx as a novel negative regulator of p53. Importantly, posttranslational modifications of p53 inhibit Daxx-p53 interaction, thereby relieving negative regulation of p53 by Daxx.The critical role of p53 in tumor suppression is manifested in frequent mutations of the p53 gene in cancers (ϳ50% of all human cancers) and in its inactivation in many other cancers by cellular or viral oncogenes and other epigenetic alterations (1). p53-deficient mice develop normally, although such mice exhibit higher incidence of tumors than their wild-type counterparts, demonstrating a critical role for p53 in suppressing tumors (2). p53 exerts its tumor suppression function by activating expression of genes involved in growth arrest and apoptosis (3, 4), and it can also induce apoptosis directly by binding to Bcl-2 family proteins and triggering cytochrome c release (5). Inducing growth arrest and cell death by p53 can impact negatively on normal cell growth and organismal development. Indeed, deletion of the mdm2 gene, whose product is a negative regulator of p53, results in embryonic lethality, but deletion of both p53 and mdm2 simultaneously completely rescues such lethal phenotype (6, 7). Thus, p53 activity must be tightly controlled under physiological conditions. In addition to MDM2, numerous cellular and viral proteins interact with p53 and these proteins can positively or negatively modulate p53-mediated biological effects. Recently, we and others demonstrated that the transcriptional corepressor Daxx interacts with p53 (8 -10), but the biological significance of this interaction remains to be explored.Daxx was initially identified as a binding protein of Fas death domain and was shown to potentiate Fas-mediated apoptosis (11). Subsequent studies implicate Daxx in promoting apoptosis in diverse stress conditions (12-1...

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Adenovirus E1B 55-Kilodalton Oncoprotein Inhibits p53 Acetylation by PCAF

Cited by 88 publications

References 71 publications

Modulation of p53 transcription regulatory activity and post-translational modification by hepatitis C virus core protein

Modulation of p53 transcription regulatory activity and post-translational modification by hepatitis C virus core protein

Identification and phylogenetic comparison of p53 in two distinct mussel species (Mytilus)

Negative Regulation of p53 Functions by Daxx and the Involvement of MDM2

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