Poliovirus Protein 3CD Is the Active Protease for Processing of the Precursor Protein P1 in vitro

Jore, J.p.m.; Geus, B. de; Jackson, R J; Pouwels, Peter H.; Enger-Valk, B.E.

doi:10.1099/0022-1317-69-7-1627

Cited by 171 publications

(127 citation statements)

References 20 publications

(30 reference statements)

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“…2 and 7). The viral proteins most directly involved in RNA synthesis are the template-and primer-dependent RNA polymerase 3D pol (8,9), the terminal protein VPg (9,10), and 3CD pro (10,11), a proteinase (12,13), and an important RNA-binding protein (14). The RNA polymerase has two distinct types of activities.…”

Section: Aaamentioning

confidence: 99%

A “Slide-back” Mechanism for the Initiation of Protein-primed RNA Synthesis by the RNA Polymerase of Poliovirus

Paul

Jiang

Mugavero

et al. 2003

Journal of Biological Chemistry

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Section: Aaamentioning

confidence: 99%

A “Slide-back” Mechanism for the Initiation of Protein-primed RNA Synthesis by the RNA Polymerase of Poliovirus

Paul

Jiang

Mugavero

et al. 2003

Journal of Biological Chemistry

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“…These strategies include synthesizing reduced amounts of the proteins by requiring read-through of leaky stop codons or ribosomal frameshifting (38,39) and differential processing of polyproteins to produce different products (9,40,41). Selective degradation of viral proteins by the ubiquitin-dependent proteolytic pathway provides a regulatory mechanism that may apply to a number of viruses.…”

Section: Degradation Of Nsp4 Is Inhibited By Dipeptides Bearingmentioning

confidence: 99%

Sindbis virus RNA polymerase is degraded by the N-end rule pathway.

Groot

Rümenapf

Kühn

et al. 1991

Proc. Natl. Acad. Sci. U.S.A.

145

117

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Upon infection of animal cells by Sindbis virus, four nonstructural (ns) proteins, termed nsPl-4 in order from 5' to 3' in the genome, are produced by posttranslational cleavage of a polyprotein. nsP4 is believed to function as the viral RNA polymerase and is short-lived in infected cells. We show here that nsP4 produced in reticulocyte lysates is degraded by the N-end rule pathway, one ubiquitin-dependent proteolytic pathway. When the N-terminal residue of nsP4 is changed by mutagenesis, the metabolic stabilities of the mutant nsP4s follow the N-end rule, in that the half-life of nsP4 bearing different N-terminal residues decreases in the order Met > Ala > Tyr 2 Phe > Arg. Addition of dipeptides Tyr-Ala, Trp-Ala, or Phe-Ala to the translation mixture inhibits degradation of Tyr-nsP4 and Phe-nsP4, but not of Arg-nsP4. Conversely, dipeptides His-Ala, Arg-Ala, and Lys-Ala inhibit the degradation of Arg-nsP4 but not of Tyr-nsP4 or Phe-nsP4. We found that there is no lysine in the first 43 residues of nsP4 that is required for its degradation, indicating that a more distal lysine functions as the ubiquitin acceptor. Strict control of nsP4 concentration appears to be an important aspect of the virus life cycle, since the concentration of nsP4 in infected cells is regulated at three levels: translation of nsP4 requlres readthrough of an opal termination codon such that it is underproduced; differential processing by the virus-encoded proteinase results in temporal regulation of nsP4; and nsP4 itself is a short-lived protein degraded by the ubiquitin-dependent N-end rule pathway.Sindbis virus, the prototype alphavirus, is an RNA animal virus whose genome is 11,703 nucleotides long. Four nonstructural (ns) proteins, called nsPl-4 from their order in the genome, are required for replication and transcription of viral RNAs and are translated as polyprotein precursors from the genomic RNA (1). We have previously reported that the synthesis of nsP4, which is thought to be the viral RNA polymerase (2-4), is regulated by at least two mechanisms in Sindbis virus. First, nsP4 is produced only upon read-through of an opal codon located at the 3' end of the nsP3 gene (5). As a consequence, nsP4 and nsP4-containing polyproteins are underproduced compared with nsP1, -2, and -3. The second regulatory mechanism involves differential processing of Sindbis polyprotein precursors by a set of virusencoded proteinases whose active site is located in the C-terminal half of nsP2 (6, 7). Polyprotein precursors containing nsP2 are all proteolytically active but differ in their cleavage-site specificities: those containing nsP1 are unable to cleave between nsP2 and nsP3, whereas only those containing nsP3 cleave between nsP3 and nsP4 (8, 9). Apparently, these differences lead to a temporal regulation of processing such that very early in infection (0-2 hr after infection) nsP4 is produced (9), whereas later in infection polyprotein P34 is produced rather than nsP4 (9-11). We have proposed that this temporal regulation ofthe relative am...

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“…This process has been extensively studied for many picornavirus superfamily members including poliovirus (Jore et al, 1988 ;Ypma-Wong et al, 1988 a ;Baum et al, 1991 ;Ha$ mmerle et al, 1991 ;Kean et al, 1991), potyviruses (Carrington et al, 1989Dougherty & Parks, 1991 ;Parks et al, 1995 ;Verchot et al, 1991), comoviruses (Dessens & Lomonossoff, 1991 ;Peters et al, b, 1995 and, to a lesser extent, nepoviruses (Demangeat et al, 1992 ;Margis et al, 1994 ; Author for correspondence : He! le ' ne Sanfaçon (at the Pacific AgriFood Research Centre).…”

Section: Introductionmentioning

confidence: 99%

Proteolytic processing of tomato ringspot nepovirus 3C-like protease precursors: definition of the domains for the VPg, protease and putative RNA-dependent RNA polymerase.

Wang

Carrier

Chisholm³

et al. 1999

Journal of General Virology

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Poliovirus Protein 3CD Is the Active Protease for Processing of the Precursor Protein P1 in vitro

Cited by 171 publications

References 20 publications

A “Slide-back” Mechanism for the Initiation of Protein-primed RNA Synthesis by the RNA Polymerase of Poliovirus

A “Slide-back” Mechanism for the Initiation of Protein-primed RNA Synthesis by the RNA Polymerase of Poliovirus

Sindbis virus RNA polymerase is degraded by the N-end rule pathway.

Proteolytic processing of tomato ringspot nepovirus 3C-like protease precursors: definition of the domains for the VPg, protease and putative RNA-dependent RNA polymerase.

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