RNA-binding properties of a translational activator, the adenovirus L4 100-kilodalton protein

Riley, David; Flint, S. J.

doi:10.1128/jvi.67.6.3586-3595.1993

Cited by 33 publications

(17 citation statements)

References 64 publications

(65 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Methylation signals were only observed in samples containing immunoprecipitated L4-100 kDa protein (Figure 4). Both L4-100 kDa and hexon, analysed in the absence of protein inhibition, were efficiently synthesized during the late phase of infection, moreover, 2100K-1 IP out of 35 S-labelled lysates revealed co-precipitation of hexon together with L4-100 kDa protein as described previously [29,30].…”

Section: Methylation Of the L4-100 Kda Protein During The Lytic Cyclesupporting

confidence: 74%

“…L4-100 kDa protein is a non-structural Ad protein abundant in the late phase of productive infection. A large proportion of the protein was found to bind viral and cellular mRNA species in the cytoplasm [30,31,33]. L4-100 kDa protein is required for efficient and selective initiation of viral late mRNA translation.…”

Section: Discussionmentioning

confidence: 99%

“…L4-100 kDa protein exhibits RNA-binding activity and apparently provides functions that increase the translation efficiency of viral late transcripts [30,31]. Protein methylation on arginine residues is a characteristic feature of many cellular and viral proteins involved in mRNA metabolism.…”

Section: L4-100 Kda Protein Is Methylated By Hprmt1 In Vitromentioning

confidence: 99%

See 2 more Smart Citations

Protein arginine methylation during lytic adenovirus infection

Kzhyshkowska

Kremmer²,

Hofmann

et al. 2004

Biochemical Journal

View full text Add to dashboard Cite

Arginine methylation of proteins affects major processes in the cell, including transcriptional regulation, mRNA metabolism, signal transduction and protein sorting. Arginine methylation of Ad (adenovirus) E1B 55-kDa-associated protein E1B-AP5 was recently described by us [Kzhyshkowska, Schutt, Liss, Kremmer, Stauber, Wolf and Dobner (2001) Biochem. J. 358, 305-314]. In this first example of protein arginine methylation analysis in Ad-infected cells, we investigated methylation of the E1B-AP5 and the viral L4-100 kDa protein. We demonstrate that E1B-AP5 methylation is enhanced during the course of infection in a cell-type-specific manner. We also show that L4-100 kDa is efficiently methylated in Ad-infected cells. L4-100 kDa formed complex with methyltransferase in vivo during productive infection, and can be methylated by HRMT1L2 (human protein arginine methyltransferase 1) in vitro. Comparative analysis of E1B-AP5 and L4-100 kDa protein methylation in Ad-infected HeLa, MCF-7 and H1299 cells revealed that the profile of protein arginine methylation correlates with the efficiency of Ad proteins production. Our results suggest that protein arginine methylation is an important host-cell function required for efficient Ad replication.

show abstract

Section: Methylation Of the L4-100 Kda Protein During The Lytic Cyclesupporting

confidence: 74%

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Protein arginine methylation during lytic adenovirus infection

Kzhyshkowska

Kremmer²,

Hofmann

et al. 2004

Biochemical Journal

View full text Add to dashboard Cite

show abstract

“…Moreover, we identified that the 100K inhibitor of gzmB was cleaved and inactivated allowing the recovery of gzmB activity. 100K is a nonstructural protein, which has essential functions in the adenovirus life cycle, including virus assembly, activation of late viral protein synthesis and inhibition of cellular protein synthesis (Cepko and Sharp, 1982;Riley and Flint, 1993;Xi et al, 2005). In addition, 100K is a gzmB substrate that potently inhibits gzmB activity (Andrade et al, 2001).…”

Section: Discussionmentioning

confidence: 99%

Granzyme H destroys the function of critical adenoviral proteins required for viral DNA replication and granzyme B inhibition

Andrade

Fellows

Jenne

et al. 2007

EMBO J

117

View full text Add to dashboard Cite

Granzymes are key components of the immune response that play important roles in eliminating host cells infected by intracellular pathogens. Several granzymes are potent inducers of cell death. However, whether granzymes use additional mechanisms to exert their antipathogen activity remains elusive. Here, we show that in adenovirusinfected cells in which granzyme B (gzmB) and downstream apoptosis pathways are inhibited, granzyme H (gzmH), an orphan granzyme without known function, directly cleaves the adenovirus DNA-binding protein (DBP), a viral component absolutely required for viral DNA replication. We directly addressed the functional consequences of the cleavage of the DBP by gzmH through the generation of a virus that encodes a gzmH-resistant DBP. This virus demonstrated that gzmH directly induces an important decay in viral DNA replication. Interestingly, gzmH also cleaves the adenovirus 100K assembly protein, a major inhibitor of gzmB, and relieves gzmB inhibition. These results provide the first evidence that granzymes can mediate antiviral activity through direct cleavage of viral substrates, and further suggest that different granzymes have synergistic functions to outflank viral defenses that block host antiviral activities.

show abstract

“…During this stage, the first protein to be synthesized is the 100 K protein, encoded by the L4 transcription unit, and this is produced in very large amounts. 30 The 100 K protein then binds to the carboxyl-terminus of eIF4G at, or near, the site that is normally occupied by the eIF4E kinase Mnk1. By competing with Mnk1 for binding, the 100 K protein acts as a direct inhibitor of Mnk1 and displaces this protein from eIF4G.…”

Section: Adenovirusmentioning

confidence: 99%

Chapter 9 Viral Strategies to Subvert the Mammalian Translation Machinery

Roberts

Jopling

Jackson

et al. 2009

Progress in Molecular Biology and Translational Science

View full text Add to dashboard Cite

Viruses do not carry their own protein biosynthesis machinery and the translation of viral proteins therefore requires that the virus usurps the machinery of the host cell. To allow optimal translation of viral proteins at the expense of cellular proteins, virus families have evolved a variety of methods to repress the host translation machinery, while allowing effective viral protein synthesis. Many viruses use noncanonical mechanisms that permit translation of their own RNAs under these conditions. Viruses have also developed mechanisms to evade host innate immune responses that would repress translation under conditions of viral infection, in particular PKR activation in response to double-stranded RNA (dsRNA). Importantly, the study of viral translation mechanisms has enormously enhanced our understanding of many aspects of the cellular protein biosynthesis pathway and its components. A number of unusual mechanisms of translation initiation that were first discovered in viruses have since been observed in cellular mRNAs, and it has become apparent that a diverse range of translation mechanisms operates in eukaryotes, allowing subtle regulation of this essential process.

show abstract

RNA-binding properties of a translational activator, the adenovirus L4 100-kilodalton protein

Abstract: The adenovirus LA 100-kDa nonstructural protein (100K protein) is required for efficient initiation of translation of viral late mRNA species during the late mRNA species during the late phase of infection (B. W.

Cited by 33 publications

References 64 publications

Protein arginine methylation during lytic adenovirus infection

Protein arginine methylation during lytic adenovirus infection

Granzyme H destroys the function of critical adenoviral proteins required for viral DNA replication and granzyme B inhibition

Chapter 9 Viral Strategies to Subvert the Mammalian Translation Machinery

Contact Info

Product

Resources

About