Requirements for E1A dependent transcription in the yeast Saccharomyces cerevisiae

Yousef, Ahmed F.; Brandl, Christopher J.; Mymryk, Joe S.

doi:10.1186/1471-2199-10-32

Cited by 6 publications

(6 citation statements)

References 56 publications

(63 reference statements)

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“…These data show, for the first time, where PKA binds on each of these unique E1As, and the observations align with previous ones for both 19). Additionally, this region of E1A has been previously shown to be associated with alterations in cAMP signaling (21)(22)(23)(24)(25) and has been characterized as being a conserved transactivation domain (7,8).…”

Section: Resultssupporting

confidence: 90%

“…A luciferase reporter driven by the previously characterized rat PEPCK promoter (36) was constructed and validated to be both cAMP inducible and PKA dependent. E1A proteins from all 7 species of HAdV could activate expression from this reporter, which was expected given E1A has multiple transactivation domains and mechanisms for inducing transcription (2,7,8,(37)(38)(39). The E1A proteins from viruses that could bind and relocalize PKA subunits (HAdV-3, -5, -9, -12) induced this reporter to the greatest extent.…”

Section: Discussionmentioning

confidence: 77%

See 1 more Smart Citation

Mimicry of Cellular A Kinase-Anchoring Proteins Is a Conserved and Critical Function of E1A across Various Human Adenovirus Species

King

Gameiro

Tessier

et al. 2018

J Virol

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The E1A proteins of the various human adenovirus (HAdV) species perform the critical task of converting an infected cell into a setting primed for virus replication. While E1A proteins differ in both sequence and mechanism, the evolutionary pressure on viruses with limited coding capacity ensures that these proteins often have significant overlap in critical functions. HAdV-5 E1A is known to use mimicry to rewire cyclic AMP (cAMP) signaling by decoupling protein kinase A (PKA) from cellular A kinase-anchoring proteins (AKAPs) and utilizing PKA to its own advantage. We show here that E1As from other species of HAdV also possess this viral AKAP (vAKAP) function and examine how they manipulate PKA. E1A from most species of HAdV examined contain a small AKAP-like motif in their N terminus which targets the docking-dimerization domain of PKA as the binding interface for a conserved protein-protein interaction. This motif is also responsible for an E1A-mediated relocalization of PKA regulatory subunits from the cytoplasm into the nucleus, with species-specific E1A proteins having preference for one particular isoform of PKA subunit over another. Importantly, we showed that these newly characterized vAKAPs can integrate into cAMP-responsive transcription as well as contribute to viral genome replication and infectious progeny production for several distinct HAdV species. These data enhance the mechanistic knowledge on how HAdV E1A manipulates cellular PKA to benefit infection. The work establishes that mimicry of AKAPs and subversion of PKA-mediated cAMP signaling are conserved features for numerous human adenoviruses. This study also highlights the molecular determinants conferring selective protein-protein interactions between distinct PKA regulatory subunits and the different E1A proteins of these viruses. Additionally, it further emphasizes the utility of using viral proteins like E1A as tools for studying the molecular biology of cellular regulatory pathways.

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Section: Resultssupporting

confidence: 90%

Section: Discussionmentioning

confidence: 77%

Mimicry of Cellular A Kinase-Anchoring Proteins Is a Conserved and Critical Function of E1A across Various Human Adenovirus Species

King

Gameiro

Tessier

et al. 2018

J Virol

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“…This unique 46 amino acid region encompasses CR3 [6]. Both the CR3 region and N-terminal 82 residues of E1A are sufficient to activate transcription when fused to a heterologous DNA binding domain [7], [8]. Although each region can separately recruit a plethora of transcriptional activators [6], [8]–[12], they function together to recruit cellular transcriptional complexes for the activation of viral transcription [5], [6], [13], [14].…”

Section: Introductionmentioning

confidence: 99%

Viral Retasking of hBre1/RNF20 to Recruit hPaf1 for Transcriptional Activation

et al. 2013

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Upon infection, human adenovirus (HAdV) must activate the expression of its early genes to reprogram the cellular environment to support virus replication. This activation is orchestrated in large part by the first HAdV gene expressed during infection, early region 1A (E1A). E1A binds and appropriates components of the cellular transcriptional machinery to modulate cellular gene transcription and activate viral early genes transcription. Previously, we identified hBre1/RNF20 as a target for E1A. The interaction between E1A and hBre1 antagonizes the innate antiviral response by blocking H2B monoubiquitination, a chromatin modification necessary for the interferon (IFN) response. Here, we describe a second distinct role for the interaction of E1A with hBre1 in transcriptional activation of HAdV early genes. Furthermore, we show that E1A changes the function of hBre1 from a ubiquitin ligase involved in substrate selection to a scaffold which recruits hPaf1 as a means to stimulate transcription and transcription-coupled histone modifications. By using hBre1 to recruit hPaf1, E1A is able to optimally activate viral early transcription and begin the cycle of viral replication. The ability of E1A to target hBre1 to simultaneously repress cellular IFN dependent transcription while activating viral transcription, represents an elegant example of the incredible economy of action accomplished by a viral regulatory protein through a single protein interaction.

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“…E1A activates transcription of the other HAdV early genes, which encode components that perform crucial tasks during infection, including inhibiting apoptosis, replicating the viral genome, suppressing immune responses, and transporting viral mRNA ( 98 – 101 ). While the transactivation ability of E1A largely maps to its N terminus and CR3 regions (both can drive reporter gene expression when fused to a heterologous DNA-binding domain) ( 102 ), E1A makes protein-protein interactions along its entire sequence that contribute to transcriptional regulation, exemplifying its modular nature.…”

Section: Data Modificationmentioning

confidence: 99%

Hacking the Cell: Network Intrusion and Exploitation by Adenovirus E1A

King

Zhang

Tessier

et al. 2018

mBio

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As obligate intracellular parasites, viruses are dependent on their infected hosts for survival. Consequently, viruses are under enormous selective pressure to utilize available cellular components and processes to their own advantage. As most, if not all, cellular activities are regulated at some level via protein interactions, host protein interaction networks are particularly vulnerable to viral exploitation. Indeed, viral proteins frequently target highly connected “hub” proteins to “hack” the cellular network, defining the molecular basis for viral control over the host. This widespread and successful strategy of network intrusion and exploitation has evolved convergently among numerous genetically distinct viruses as a result of the endless evolutionary arms race between pathogens and hosts. Here we examine the means by which a particularly well-connected viral hub protein, human adenovirus E1A, compromises and exploits the vulnerabilities of eukaryotic protein interaction networks. Importantly, these interactions identify critical regulatory hubs in the human proteome and help define the molecular basis of their function.

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Requirements for E1A dependent transcription in the yeast Saccharomyces cerevisiae

Cited by 6 publications

References 56 publications

Mimicry of Cellular A Kinase-Anchoring Proteins Is a Conserved and Critical Function of E1A across Various Human Adenovirus Species

Mimicry of Cellular A Kinase-Anchoring Proteins Is a Conserved and Critical Function of E1A across Various Human Adenovirus Species

Viral Retasking of hBre1/RNF20 to Recruit hPaf1 for Transcriptional Activation

Hacking the Cell: Network Intrusion and Exploitation by Adenovirus E1A

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