Efficient Cleavage of Ribosome-Associated Poly(A)-Binding Protein by Enterovirus 3C Protease

Kuyumcu-Martinez, N. Muge; Joachims, Michelle L.; Lloyd, Richard E.

doi:10.1128/jvi.76.5.2062-2074.2002

Cited by 124 publications

(151 citation statements)

References 75 publications

(82 reference statements)

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“…1C), whereas potent hydrolysis was found using this antibody in cells trans-fected with pTM1-3C, pTM1-2A, or pTM1-HIV-1PR (24). In this regard, PV 2A pro exhibited low proteolytic activity against PABP (25,10). Two lower polypeptides were found in control as well as in 2A…”

Section: Transfection Of Hela Cells With Mrnasmentioning

confidence: 96%

“…Cleavage of both eIF4GI and eIF4GII strongly blocked the initiation of de novo synthesized mRNAs (17). In addition, PV and Coxsackievirus 2A pro and 3C pro are able to cleave PABP during infection (10). More recently, it has been reported that hydrolysis of PABP by 3C pro in the absence of eIF4G degradation blocks the translation of endogenous mRNAs in HeLa cell extracts (18).…”

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confidence: 99%

“…More recently, it has been reported that hydrolysis of PABP by 3C pro in the absence of eIF4G degradation blocks the translation of endogenous mRNAs in HeLa cell extracts (18). 3C pro preferentially hydrolyzed the PABP associated with the translational machinery, although the hydrolysis of PABP did not correlate with the shutoff of cellular translation in PV-infected cells (10). Therefore, the individual contribution of eIF4GI, eIF4GII, and PABP proteolysis to the shutoff of cellular protein synthesis needs further investigation.…”

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confidence: 99%

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Differential Cleavage of eIF4GI and eIF4GII in Mammalian Cells

Castelló

Álvarez

Carrasco

2006

Journal of Biological Chemistry

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Two isoforms of the translation initiation factor eIF4G, eIF4GI and eIF4GII, have been described in eukaryotic cells. The exact function of each isoform during the initiation of protein synthesis is still under investigation. We have developed an efficient and reliable method of expressing poliovirus 2Apro, which differentially proteolyzes eIF4GI and eIF4GII in a timeand dose-dependent manner. This system is based on the electroporation of an in vitro transcribed mRNA that contains the encephalomyocarditis virus internal ribosome entry site followed by the sequence of poliovirus 2Apro. In contrast to HeLa cells, expression of this protease in BHK-21 cells induces delayed hydrolysis kinetics of eIF4GI with respect to eIF4GII. Moreover, under these conditions the polyadenylate binding protein is not cleaved. Interestingly, translation of de novo synthesized luciferase mRNA is highly dependent on eIF4GI integrity, whereas ongoing translation is inhibited at the same time as eIF4GII cleavage. Moreover, reinitiation of a preexisting mRNA translation after polysome run-off is dependent on the integrity of eIF4GII. Notably, de novo translation of heat shock protein 70 mRNA depends little on eIF4GI integrity but is more susceptible to eIF4GII hydrolysis. Finally, translation of an mRNA containing encephalomyocarditis virus internal ribosome entry site when the two isoforms of eIF4G are differentially hydrolyzed has been examined.

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Section: Transfection Of Hela Cells With Mrnasmentioning

confidence: 96%

mentioning

confidence: 99%

mentioning

confidence: 99%

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Differential Cleavage of eIF4GI and eIF4GII in Mammalian Cells

Castelló

Álvarez

Carrasco

2006

Journal of Biological Chemistry

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“…In animal cells, PABP is cleaved by proteinases of picornaviruses (Joachims et al, 1999;Kerekatte et al, 1999;Kuyumcu-Martinez et al, 2002, 2004bRodriguez Pulido et al, 2007;Zhang et al, 2007), caliciviruses (Kuyumcu-Martinez et al, 2004a) and retroviruses (Alvarez et al, 2006). The resultant cleavage leads to host translational shutdown (Joachims et al, 1999; KuyumcuMartinez et al, 2004a, b;Zhang et al, 2007).…”

Section: Introductionmentioning

confidence: 99%

Arabidopsis thaliana class II poly(A)-binding proteins are required for efficient multiplication of turnip mosaic virus

Dufresne

Ubalijoro

Fortin

et al. 2008

Journal of General Virology

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The poly(A)-binding protein (PABP) is an important translation initiation factor that binds to the polyadenylated 39 end of mRNA. We have previously shown that PABP2 interacts with the RNAdependent RNA polymerase (RdRp) and VPg-Pro of turnip mosaic virus (TuMV) within virusinduced vesicles. At least eight PABP isoforms are produced in Arabidopsis thaliana, three of which (PABP2, PABP4 and PABP8) are highly and broadly expressed and probably constitute the bulk of PABP required for cellular functions. Upon TuMV infection, an increase in protein and mRNA expression from PAB2, PAB4 and PAB8 genes was recorded. In vitro binding assays revealed that RdRp and the viral genome-linked protein (VPg-Pro) interact preferentially with PABP2 but are also capable of interaction with one or both of the other class II PABPs (i.e. PABP4 and PABP8). To assess whether PABP is required for potyvirus replication, A. thaliana single and double pab knockouts were isolated and inoculated with TuMV. All lines showed susceptibility to TuMV. However, when precise monitoring of viral RNA accumulation was performed, it was found to be reduced by 2.2-and 3.5-fold in pab2 pab4 and pab2 pab8 mutants, respectively, when compared with wild-type plants. PABP levels were most significantly reduced in the membrane-associated fraction in both of these mutants. TuMV mRNA levels thus correlated with cellular PABP concentrations in these A. thaliana knockout lines. These data provide further support for a role of PABP in potyvirus replication. INTRODUCTIONThe poly(A)-binding protein (PABP) is an abundant translation initiation factor in the cell that binds to the polyadenylated 39 end of mRNA. Its interaction with the eukaryotic translation initiation factor 4F complex (composed of the eIF4E, eIF4A and eIF4G proteins), which is bound to the 59 cap structure of the mRNA, results in the formation of a protein bridge that brings the 59 and 39 termini of the mRNA into proximity. This leads to a synergistic enhancement of translation (Sachs, 2000;Wells et al., 1998). PABP is also important for stability (BehmAnsmant et al., 2007;Parker & Song, 2004), biogenesis (Amrani et al., 1997;Brown & Sachs, 1998) and nuclear export of cellular mRNAs (Brune et al., 2005).Multiple PABP isoforms are normally found in animals and plants (Mangus et al., 2003). Eight PABP genes have been identified in Arabidopsis thaliana (Belostotsky, 2003).The corresponding proteins are divided into four classes based on gene expression and similarity. Class II genes (PAB2, PAB4 and PAB8) are highly and broadly expressed and probably encode the bulk of PABP required for cellular functions (Belostotsky, 2003).In animal cells, PABP is cleaved by proteinases of picornaviruses (Joachims et al., 1999;Kerekatte et al., 1999;Kuyumcu-Martinez et al., 2002, 2004bRodriguez Pulido et al., 2007;Zhang et al., 2007), caliciviruses (Kuyumcu-Martinez et al., 2004a) and retroviruses (Alvarez et al., 2006). The resultant cleavage leads to host translational shutdown (Joachims et al., 1999; KuyumcuMartinez ...

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“…In vitro cleavage assays using purified recombinant viral proteases were performed as previously described (31). Briefly, 100 ng of 2A pro or 3C pro or 300 ng of 3CD pro was incubated with 100 g of HeLa cell S10 extract in cleavage buffer (100 mM NaCl, 5 mM MgCl 2 , 10 mM HEPES-KOH, pH 7.4) for 30 min at 37°C.…”

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confidence: 99%

Proteolytic Cleavage of the Catalytic Subunit of DNA-Dependent Protein Kinase during Poliovirus Infection

Graham

Gustin

Rivera

et al. 2004

J Virol

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DNA-dependent protein kinase (DNA-PK) is a serine/threonine kinase that has critical roles in DNA double-strand break repair, as well as B-and T-cell antigen receptor rearrangement. The DNA-PK enzyme consists of the Ku regulatory subunit and a 450-kDa catalytic subunit termed DNA-PK CS . Both of these subunits are autoantigens associated with connective tissue diseases such as systemic lupus erythematosus (SLE) and scleroderma. In this report, we show that DNA-PK CS is cleaved during poliovirus infection of HeLa cells. Cleavage was visible as early as 1.5 h postinfection (hpi) and resulted in an approximately 40% reduction in the levels of native protein by 5.5 hpi. Consistent with this observation, the activity of the DNA-PK CS enzyme was also reduced during viral infection, as determined by immunoprecipitation kinase assays. Although it has previously been shown that DNA-PK CS is a substrate of caspase-3 in vitro, the protein was still cleaved during poliovirus infection of the caspase-3-deficient MCF-7 cell line. Cleavage was not prevented by infection in the presence of a soluble caspase inhibitor, suggesting that cleavage in vivo was independent of host caspase activation. DNA-PK CS is directly cleaved by a picornaviral 2A protease in vitro, producing a fragment similar in size to the cleavage product observed in vivo. Taken together, our results indicate that DNA-PK CS is cleaved by the 2A protease during poliovirus infection. Proteolytic cleavage of DNA-PK CS during poliovirus infection may contribute to inhibition of host immune responses. Furthermore, cleavage of autoantigens by viral proteases may target these proteins for the autoimmune response by generating novel, or "immunocryptic," protein fragments.

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Efficient Cleavage of Ribosome-Associated Poly(A)-Binding Protein by Enterovirus 3C Protease

Cited by 124 publications

References 75 publications

Differential Cleavage of eIF4GI and eIF4GII in Mammalian Cells

Differential Cleavage of eIF4GI and eIF4GII in Mammalian Cells

Arabidopsis thaliana class II poly(A)-binding proteins are required for efficient multiplication of turnip mosaic virus

Proteolytic Cleavage of the Catalytic Subunit of DNA-Dependent Protein Kinase during Poliovirus Infection

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