Requirement of Sur2 for Efficient Replication of Mouse Adenovirus Type 1

Fang, Lei; Stevens, Jennitte; Berk, Arnold; Spindler, Katherine R.

doi:10.1128/jvi.78.23.12888-12900.2004

Cited by 16 publications

(39 citation statements)

References 64 publications

(81 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…A recent report has shown that murine Sur2 is needed for efficient replication of mouse adenovirus type 1 in mouse embryo fibroblasts (48). Sur2 is a subunit of the transcription mediator complex, which bridges transcription regulators to RNA polymerase II.…”

Section: Discussionmentioning

confidence: 99%

Decreased Replication Ability of E1-Deleted Adenoviruses Correlates with Increased Brain Tumor Malignancy

Ghosh

Duigou

2005

Cancer Research

View full text Add to dashboard Cite

E1 region replacement adenoviruses are replication defective and are propagated in cells providing adenovirus E1A and E1B proteins. Although they are being developed for antitumor therapies, the proliferative behaviors of these viruses in normal brain tissues or in brain tumors are unknown. To address this, freshly cultured cells from normal human brain and common brain tumors (astrocytomas and meningiomas) were infected using wild-type species C adenoviruses and adenoviruses missing E1A (H5dl312) or E1A plus E1B (H5dl434). Viral DNA replication, late viral protein expression, and production of infectious progeny were characterized. Wild-type adenoviruses grew efficiently in normal brain and brain tumor cells. In comparison, E1-deleted adenovirus DNA replication was delayed and lower in cells derived from normal brain tissues, meningiomas, and low-grade astrocytomas. However, in contrast, E1-deleted adenovirus DNA replication did not occur or was extremely low in cells derived from malignancy grade III and IV astrocytic tumors. Because wild-type adenoviruses infected and replicated in all cells, the malignancy grade-based differential E1-deleted adenovirus DNA replication was not explained by differential virus uptake. Infectious H5dl312 and H5dl434 production correlated with viral DNA replication. Compared with a 5-day average for wild-type infections, advanced cytopathology was noted f4 weeks after H5dl312 or H5dl434 infection of meningioma, astrocytoma, and normal brain cells. Cytopathology was not observed after H5dl312 or H5dl434 infection of glioblastoma, anaplastic astrocytoma, and gliosarcoma cells. Because of this tumor grade-based differential growth, the E1-deleted adenoviruses may represent novel tools for studies of brain tumor malignancy. (Cancer Res 2005; 65(19): 8936-43)

show abstract

Section: Discussionmentioning

confidence: 99%

Decreased Replication Ability of E1-Deleted Adenoviruses Correlates with Increased Brain Tumor Malignancy

Ghosh

Duigou

2005

Cancer Research

View full text Add to dashboard Cite

show abstract

“…However, after infection with a single virion, the level of early gene transcription is too low to support viral replication unless E1A CR3 turns up the rate of reinitiation by 5-20-fold, depending on the early viral promoter. Similarly murine adenovirus I, which encodes an E1A with a homolgous CR3 that interacts with murine MED23, requires MED23 for high rate transcription of its early genes at low multiplicity of infection (Fang et al, 2004).…”

Section: E1a Conserved Region 3 Activation Of Early Viral Gene Expresmentioning

confidence: 99%

Recent lessons in gene expression, cell cycle control, and cell biology from adenovirus

2005

View full text Add to dashboard Cite

Adenovirus continues to be an important model system for investigating basic aspects of cell biology. Interactions of several cellular proteins with E1A conserved regions (CR) 1 and 2, and inhibition of apoptosis by E1B proteins are required for oncogenic transformation. CR2 binds RB family members, de-repressing E2F transcription factors, thus activating genes required for cell cycling. E1B-19K is a BCL2 homolog that binds and inactivates proapoptotic BAK and BAX. E1B-55K binds p53, inhibiting its transcriptional activation function. In productively infected cells, E1B-55K and E4orf6 assemble a ubiquitin ligase with cellular proteins Elongins B and C, Cullin 5 and RBX1 that polyubiquitinates p53 and one or more subunits of the MRN complex involved in DNA doublestrand break repair, directing them to proteosomal degradation. E1A CR3 activates viral transcription by interacting with the MED23 Mediator subunit, stimulating preinitiation complex assembly on early viral promoters and probably also the rate at which they initiate transcription. The viral E1B-55K/E4orf6 ubiquitin ligase is also required for efficient viral late protein synthesis in many cell types, but the mechanism is not understood. E1A CR1 binds several chromatin-modifying complexes, but how this contributes to stimulation of cellular DNA synthesis and transformation is not clear. E1A CR4 binds the CtBP corepressor, but the mechanism by which this modulates the frequency of transformation remains to be determined. Clearly, adenovirus has much left to teach us about fundamental cellular processes.

show abstract

“…The CR3 regions of several HAdv types have also been reported to bind with MED23 (22). In Med23 KO cells infected with the mouse adenovirus 1 (MAdv 1) (which codes for an E1A protein that contains a CR3 domain related to HAdv5 CR3), the levels of early gene transcription were retarded, suggesting that Med23 plays an important role in the transcriptional activity of MAdv E1A (23). Although MED23 has been shown to promote transcription at the recruitment and postrecruitment steps in transcriptional initiation by EGR 1 (24), the precise role of MED23 in the transcriptional activation of HAdv5 early genes remains to be elucidated.…”

mentioning

confidence: 99%

Adenovirus L-E1A Activates Transcription through Mediator Complex-Dependent Recruitment of the Super Elongation Complex

Vijayalingam

Chinnadurai

2013

J Virol

View full text Add to dashboard Cite

The adenovirus large E1A (L-E1A) protein is a prototypical transcriptional activator, and it functions through the action of a conserved transcriptional activation domain, CR3. CR3 interacts with a mediator subunit, MED23, that has been linked to the transcriptional activity of CR3. Our unbiased proteomic analysis revealed that human adenovirus 5 (HAdv5) L-E1A was associated with many mediator subunits. In MED23-depleted cells and in Med23 knockout (KO) cells, L-E1A was deficient in association with other mediator subunits, suggesting that MED23 links CR3 with the mediator complex. Short interfering RNA (siRNA)-mediated depletion of several mediator subunits suggested differential effects of various subunits on transcriptional activation of HAdv5 early genes. In addition to MED23, mediator subunits such as MED14 and MED26 were also essential for the transcription of HAdv5 early genes. The L-E1A proteome contained MED26-associated super elongation complex. The catalytic component of the elongation complex, CDK9, was important for the transcriptional activity of L-E1A and HAdv5 replication. Our results suggest that L-E1A-mediated transcriptional activation involves a transcriptional elongation step, like HIV Tat, and constitutes a therapeutic target for inhibition of HAdv replication. Adenovirus E1A is the immediate-early viral gene that plays an essential role in viral replication by driving quiescent host cells into the cell cycle and by transcriptional activation of other viral early genes (reviewed in references 1 and 2). The E1A gene codes for two major protein isoforms, designated small E1A (S-E1A) and large E1A (L-E1A). The two protein isoforms differ only by the presence of a 46-amino-acid unique region (designated conserved region 3, or CR3) that is conserved among different adenovirus serotypes. While both E1A proteins can promote proliferation of quiescent target cells by activation of S phase genes, L-E1A is required for transcriptional activation of other viral early genes (3, 4). The role of CR3 in the transcriptional activation of viral early genes was established on the basis of results that showed a substantial decrease in expression of viral early genes in cells infected with different human adenovirus 5 (HAdv5) mutants with lesions in CR3 (3, 4). Further, protein microinjection and transcriptional tethering studies also demonstrated that a synthetic CR3 peptide (5, 6) or a CR3-Gal4 DNA binding domain (DBD) chimeric gene (7,8) can activate viral early promoters. Although E1A CR3 constitutes a powerful trans-activation domain of a viral transcriptional activator and has been intensely investigated as a model trans-activation domain, the mechanism by which it mediates transcriptional activation of other viral early genes remains incompletely understood. The N-terminal 40-aminoacid region of CR3 which forms the C-4 zinc finger (9) has been postulated to function as the trans-activation subdomain, as it is sufficient for transcriptional activation as a Gal4 DNA binding domain fusion protein. The N-te...

show abstract

Requirement of Sur2 for Efficient Replication of Mouse Adenovirus Type 1

Cited by 16 publications

References 64 publications

Decreased Replication Ability of E1-Deleted Adenoviruses Correlates with Increased Brain Tumor Malignancy

Decreased Replication Ability of E1-Deleted Adenoviruses Correlates with Increased Brain Tumor Malignancy

Recent lessons in gene expression, cell cycle control, and cell biology from adenovirus

Adenovirus L-E1A Activates Transcription through Mediator Complex-Dependent Recruitment of the Super Elongation Complex

Contact Info

Product

Resources

About