The Human Adenovirus Type 5 L4 Promoter Is Negatively Regulated by TFII-I and L4-33K

Wright, Jordan; Atwan, Zeenah Weheed; Morris, Susan; Leppard, Keith N.

doi:10.1128/jvi.00683-15

Cited by 9 publications

(13 citation statements)

References 52 publications

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“…Two recent proteomic analyses of proteins associated with nascent cellular DNA also identified TFII-I among enriched factors, and depletion suggested a potential role in DNA replication (19,20). In addition, TFII-I was identified as a substrate for post-translational SUMOylation induced by the Ad5 E4orf3 protein (90), and as a negative regulator of the viral L4 promoter (91,92). TFII-I was recently shown to target the CCCTC-binding factor CTCF to gene promoters (93), and because CTCF may represent a common repressor of DNA viruses (94), TFII-I may be targeted as a means of preventing repression.…”

Section: Discussionmentioning

confidence: 96%

Identifying Host Factors Associated with DNA Replicated During Virus Infection

Reyes

Kulej

Pancholi

et al. 2017

Molecular & Cellular Proteomics

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Viral DNA genomes replicating in cells encounter a myriad of host factors that facilitate or hinder viral replication. Viral proteins expressed early during infection modulate host factors interacting with viral genomes, recruiting proteins to promote viral replication, and limiting access to antiviral repressors. Although some host factors manipulated by viruses have been identified, we have limited knowledge of pathways exploited during infection and how these differ between viruses. To identify cellular processes manipulated during viral replication, we defined proteomes associated with viral genomes during infection with adenovirus, herpes simplex virus and vaccinia virus. We compared enrichment of host factors between virus proteomes and confirmed association with viral genomes and replication compartments. Using adenovirus as an illustrative example, we uncovered host factors deactivated by early viral proteins, and identified a subgroup of nucleolar proteins that aid virus replication. Our data sets provide valuable resources of virus-host interactions that affect proteins on viral genomes.

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Section: Discussionmentioning

confidence: 96%

Identifying Host Factors Associated with DNA Replicated During Virus Infection

Reyes

Kulej

Pancholi

et al. 2017

Molecular & Cellular Proteomics

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“…TFII-I can function as part of the basal transcription machinery and as a signal-inducible transcriptional activator or repressor ( 17 ). TFII-I was recently shown to be a negative regulator of the Ad5 intermediate-phase promoter, L4P, for which E4-ORF3 is an activator in reporter assays ( 18 ). Posttranslational modification of TFII-I is critical for its transcriptional activity at several promoters.…”

Section: Introductionmentioning

confidence: 99%

The Adenovirus E4-ORF3 Protein Stimulates SUMOylation of General Transcription Factor TFII-I to Direct Proteasomal Degradation

Bridges

Sohn

Wright

et al. 2016

mBio

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Modulation of host cell transcription, translation, and posttranslational modification processes is critical for the ability of many viruses to replicate efficiently within host cells. The human adenovirus (Ad) early region 4 open reading frame 3 (E4-ORF3) protein forms unique inclusions throughout the nuclei of infected cells and inhibits the antiviral Mre11-Rad50-Nbs1 DNA repair complex through relocalization. E4-ORF3 also induces SUMOylation of Mre11 and Nbs1. We recently identified additional cellular targets of E4-ORF3 and found that E4-ORF3 stimulates ubiquitin-like modification of 41 cellular proteins involved in a wide variety of processes. Among the proteins most abundantly modified in an E4-ORF3-dependent manner was the general transcription factor II–I (TFII-I). Analysis of Ad-infected cells revealed that E4-ORF3 induces TFII-I relocalization and SUMOylation early during infection. In the present study, we explored the relationship between E4-ORF3 and TFII-I. We found that Ad infection or ectopic E4-ORF3 expression leads to SUMOylation of TFII-I that precedes a rapid decline in TFII-I protein levels. We also show that E4-ORF3 is required for ubiquitination of TFII-I and subsequent proteasomal degradation. This is the first evidence that E4-ORF3 regulates ubiquitination. Interestingly, we found that E4-ORF3 modulation of TFII-I occurs in diverse cell types but only E4-ORF3 of Ad species C regulates TFII-I, providing critical insight into the mechanism by which E4-ORF3 targets TFII-I. Finally, we show that E4-ORF3 stimulates the activity of a TFII-I-repressed viral promoter during infection. Our results characterize a novel mechanism of TFII-I regulation by Ad and highlight how a viral protein can modulate a critical cellular transcription factor during infection.

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“…While this last site was previously predicted to lead to the expression of a small 42 amino acid ORF [53], we propose that this transcript instead primarily encodes for pVIII with a small upstream ORF, as it is over five times as abundant as the canonical pVIII spliced RNA. It should be noted that we did not detect the presence of a putative L4 intermediate promoter TSS at either 12 or 24 hpi [45,77,78]. One hypothesis is that the sequence detected in L4-100K that is necessary for early expression of L4-22K and L4-33K might instead encode for a cis -regulatory element that mediates the early accumulation of these two products produced from the major late promoter.…”

Section: Discussionmentioning

confidence: 96%

Novel splicing and open reading frames revealed by long-read direct RNA sequencing of adenovirus transcripts

Hayer²,

Depledge

et al. 2019

Preprint

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20Adenovirus is a common human pathogen that relies on host cell processes for production 21 and processing of viral RNA. Although adenoviral promoters, splice junctions, and cleavage and 22 proteins by linking separate gene transcription units. Our work highlights how long-read 33 sequencing technologies can reveal further complexity within viral transcriptomes. : bioRxiv preprint another multifunctional protein that can cooperate with E1A to alter cellular gene expression 61 downstream of p53 as well as form the targeting component of a viral ubiquitin ligase [18][19][20][21][22][23]. 62The remaining early transcription units are all transcriptionally activated by E1A and encode for 63 products of related function. The E2 region on the reverse strand of the AdV genome has both an 64 early and a late promoter, as well as two distinct polyadenylation sites, leading to upstream E2A 65 and downstream E2B transcripts [24]. E2A encodes for the viral DNA-binding protein (DBP), while 66 alternative splicing to E2B encodes for the protein-priming terminal protein (pTP) as well as the 67AdV DNA polymerase (AdPol) [25][26][27]. The E3 region encoded on the top strand also has two 68

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The Human Adenovirus Type 5 L4 Promoter Is Negatively Regulated by TFII-I and L4-33K

Cited by 9 publications

References 52 publications

Identifying Host Factors Associated with DNA Replicated During Virus Infection

Identifying Host Factors Associated with DNA Replicated During Virus Infection

The Adenovirus E4-ORF3 Protein Stimulates SUMOylation of General Transcription Factor TFII-I to Direct Proteasomal Degradation

Novel splicing and open reading frames revealed by long-read direct RNA sequencing of adenovirus transcripts

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