Adenovirus-5 E1A: paradox and paradigm

Frisch, Steven M.; Mymryk, Joe S.

doi:10.1038/nrm827

Cited by 269 publications

(271 citation statements)

References 129 publications

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“…E1A CR1 and N-terminal region bind to p300 (Stein et al, 1990) and CBP (Arany et al, 1995), multifunctional proteins, interacting with a number of transcriptional factors and endowed with histone acetyltransferase (HAT) activity (Iyer et al, 2004). The E1A binding alters the activity of these proteins (Frisch and Mymryk, 2002) with effects also on the expression or function of the pocket proteins. In differentiating mouse myoblasts, E1A abrogates the induction of the expression of RB1 by a mechanism that is p300/CBP dependent (Martelli et al, 1994;Magenta et al, 2003).…”

Section: Adenovirus Early-region 1amentioning

confidence: 99%

Retinoblastoma family proteins as key targets of the small DNA virus oncoproteins

Mileo²,

2006

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Section: Adenovirus Early-region 1amentioning

confidence: 99%

Retinoblastoma family proteins as key targets of the small DNA virus oncoproteins

Mileo²,

2006

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“…(b) Adenovirus dl1520/ÀE2a DNA transduced into Saos2 andproteins, including pRb and p300, to reprogram cellular gene expression and cell cycle regulation. 49 E1A can force host cells into S phase to provide an optimal cellular environment for viral replication. Thus, we further investigate whether the cell cycle progression is correlated with cancer selective replication of dl1520.…”

Section: Adenoviruses-induced Cell Cycle Changes In Hep3b and Saos2 Cmentioning

confidence: 99%

Selective replication of E1B55K-deleted adenoviruses depends on enhanced E1A expression in cancer cells

Zheng

et al. 2005

Cancer Gene Ther

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E1B55K-deleted dl1520 could selectively replicate in cancer cells and has been used in clinical trials as an antitumor agent. The mechanism of virus selective replication in cancer cells, including a possible role of p53, is unclear. Studies with established cancer cell lines have demonstrated that some cancer cells are resistant to dl1520 replication, regardless of the p53 status. Hep3B cells supported the E1b-deleted adenoviruses to replicate, whereas Saos2 cells were resistant to viral replication. We applied p53-null Hep3B and Saos2 cells as models to clarify the replication ability of E1B55K-deleted adenoviruses with different expression levels of E1a. We show that lower E1A expression in Saos2 may be the reason for the poor replication in some cancer cells due to the fact that E1a promoter was less activated in Saos2 than in Hep3B. We also demonstrate that the E1B55K protein can increase E1A expression in Saos2 cells for efficient virus replication. In addition, the upstream regions of the E1a promoter have transcriptional activity in Hep3B cells but not in Saos2 cells. The viral E1B55K protein may activate cancer cellular factor(s) that targets the upstream regions of the E1a gene to increase its expression. This is the first study demonstrating that E1B55K protein affects the E1A production levels that is related to cancer selective replication. Our studies have suggested that increase of E1A expression from E1b-deleted adenoviruses may enhance killing cancer cells that otherwise are resistant to viral replication.

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“…Oncogenic transformation directly reflects the fundamental changes made to the cellular protein interaction network by virally encoded hub proteins in the infected cell. E1A is a key molecular hub in HAd (Frisch and Mymryk, 2002;Pelka et al, 2008). Sequence comparisons of the E1A proteins of numerous HAds identified four regions of sequence similarity, designated CR1-4 (Avvakumov et al, 2002(Avvakumov et al, , 2004.…”

Section: Introductionmentioning

confidence: 99%

Identification of a molecular recognition feature in the E1A oncoprotein that binds the SUMO conjugase UBC9 and likely interferes with polySUMOylation

et al. 2010

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Hub proteins have central roles in regulating cellular processes. By targeting a single cellular hub, a viral oncogene may gain control over an entire module in the cellular interaction network that is potentially comprised of hundreds of proteins. The adenovirus E1A oncoprotein is a viral hub that interacts with many cellular hub proteins by short linear motifs/molecular recognition features (MoRFs). These interactions transform the architecture of the cellular protein interaction network and virtually reprogram the cell. To identify additional MoRFs within E1A, we screened portions of E1A for their ability to activate yeast pseudohyphal growth or differentiation. This identified a novel functional region within E1A conserved region 2 comprised of the sequence EVIDLT. This MoRF is necessary and sufficient to bind the N-terminal region of the SUMO conjugase UBC9, which also interacts with SUMO noncovalently and is involved in polySUMOylation. Our results suggest that E1A interferes with polySUMOylation, but not with monoSUMOylation. These data provide the first insight into the consequences of the interaction of E1A with UBC9, which was initially described in 1996. We further demonstrate that polySUMOylation regulates pseudohyphal growth and promyelocytic leukemia body reorganization by E1A. In conclusion, the interaction of the E1A oncogene with UBC9 mimics the normal binding between SUMO and UBC9 and represents a novel mechanism to modulate polySUMOylation.

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Adenovirus-5 E1A: paradox and paradigm

Cited by 269 publications

References 129 publications

Retinoblastoma family proteins as key targets of the small DNA virus oncoproteins

Retinoblastoma family proteins as key targets of the small DNA virus oncoproteins

Selective replication of E1B55K-deleted adenoviruses depends on enhanced E1A expression in cancer cells

Identification of a molecular recognition feature in the E1A oncoprotein that binds the SUMO conjugase UBC9 and likely interferes with polySUMOylation

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