The Experts below are selected from a list of 21480 Experts worldwide ranked by ideXlab platform
Göran Akusjärvi - One of the best experts on this subject based on the ideXlab platform.
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Review Regulation of Human Adenovirus Alternative RNA Splicing by the Adenoviral L4-33K and L4-22K Proteins
2016Co-Authors: Roberta Biasiotto, Göran AkusjärviAbstract:Abstract: Adenovirus makes extensive use of alternative RNA splicing to produce a complex set of spliced viral mRNAs. Studies aimed at characterizing the interactions between the virus and the host cell RNA splicing machinery have identified three viral Proteins of special significance for the control of late viral gene expression: L4-33K, L4-22K, and E4-ORF4. L4-33K is a viral alternative RNA splicing factor that controls L1 alternative splicing via an interaction with the cellular Protein kinases Protein Kinase A (PKA) and DNA-dependent Protein kinase (DNA-PK). L4-22K is a viral transcription factor that also has been implicated in the splicing of a subset of late viral mRNAs. E4-ORF4 is a viral Protein that binds the cellular Protein phosphatase IIA (PP2A) and controls Serine/Arginine (SR)-rich Protein activity by inducing SR Protein Dephosphorylation. The L4-33K, and most likely also the L4-22K Protein, are highly phosphorylated in vivo. Here we will review the function of these viral Proteins in the post-transcriptional control of adenoviral gene expression and further discuss the significance of potential Protein kinases phosphorylating the L4-33K and/or L4-22K Proteins
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Regulation of Human Adenovirus Alternative RNA Splicing by the Adenoviral L4-33K and L4-22K Proteins
2015Co-Authors: Roberta Biasiotto, Göran AkusjärviAbstract:Adenovirus makes extensive use of alternative RNA splicing to produce a complex set of spliced viral mRNAs. Studies aimed at characterizing the interactions between the virus and the host cell RNA splicing machinery have identified three viral Proteins of special significance for the control of late viral gene expression: L4-33K, L4-22K, and E4-ORF4. L4-33K is a viral alternative RNA splicing factor that controls L1 alternative splicing via an interaction with the cellular Protein kinases Protein Kinase A (PKA) and DNA-dependent Protein kinase (DNA-PK). L4-22K is a viral transcription factor that also has been implicated in the splicing of a subset of late viral mRNAs. E4-ORF4 is a viral Protein that binds the cellular Protein phosphatase IIA (PP2A) and controls Serine/Arginine (SR)-rich Protein activity by inducing SR Protein Dephosphorylation. The L4-33K, and most likely also the L4-22K Protein, are highly phosphorylated in vivo. Here we will review the function of these viral Proteins in the post-transcriptional control of adenoviral gene expression and further discuss the significance of potential Protein kinases phosphorylating the L4-33K and/or L4-22K Proteins.
Roberta Biasiotto - One of the best experts on this subject based on the ideXlab platform.
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Review Regulation of Human Adenovirus Alternative RNA Splicing by the Adenoviral L4-33K and L4-22K Proteins
2016Co-Authors: Roberta Biasiotto, Göran AkusjärviAbstract:Abstract: Adenovirus makes extensive use of alternative RNA splicing to produce a complex set of spliced viral mRNAs. Studies aimed at characterizing the interactions between the virus and the host cell RNA splicing machinery have identified three viral Proteins of special significance for the control of late viral gene expression: L4-33K, L4-22K, and E4-ORF4. L4-33K is a viral alternative RNA splicing factor that controls L1 alternative splicing via an interaction with the cellular Protein kinases Protein Kinase A (PKA) and DNA-dependent Protein kinase (DNA-PK). L4-22K is a viral transcription factor that also has been implicated in the splicing of a subset of late viral mRNAs. E4-ORF4 is a viral Protein that binds the cellular Protein phosphatase IIA (PP2A) and controls Serine/Arginine (SR)-rich Protein activity by inducing SR Protein Dephosphorylation. The L4-33K, and most likely also the L4-22K Protein, are highly phosphorylated in vivo. Here we will review the function of these viral Proteins in the post-transcriptional control of adenoviral gene expression and further discuss the significance of potential Protein kinases phosphorylating the L4-33K and/or L4-22K Proteins
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Regulation of Human Adenovirus Alternative RNA Splicing by the Adenoviral L4-33K and L4-22K Proteins
2015Co-Authors: Roberta Biasiotto, Göran AkusjärviAbstract:Adenovirus makes extensive use of alternative RNA splicing to produce a complex set of spliced viral mRNAs. Studies aimed at characterizing the interactions between the virus and the host cell RNA splicing machinery have identified three viral Proteins of special significance for the control of late viral gene expression: L4-33K, L4-22K, and E4-ORF4. L4-33K is a viral alternative RNA splicing factor that controls L1 alternative splicing via an interaction with the cellular Protein kinases Protein Kinase A (PKA) and DNA-dependent Protein kinase (DNA-PK). L4-22K is a viral transcription factor that also has been implicated in the splicing of a subset of late viral mRNAs. E4-ORF4 is a viral Protein that binds the cellular Protein phosphatase IIA (PP2A) and controls Serine/Arginine (SR)-rich Protein activity by inducing SR Protein Dephosphorylation. The L4-33K, and most likely also the L4-22K Protein, are highly phosphorylated in vivo. Here we will review the function of these viral Proteins in the post-transcriptional control of adenoviral gene expression and further discuss the significance of potential Protein kinases phosphorylating the L4-33K and/or L4-22K Proteins.
Michael G Katze - One of the best experts on this subject based on the ideXlab platform.
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the direct binding of the catalytic subunit of Protein phosphatase 1 to the pkr Protein kinase is necessary but not sufficient for inactivation and disruption of enzyme dimer formation
2002Co-Authors: Seng Lai Tan, Semih U Tareen, Mark W Melville, Collin M Blakely, Michael G KatzeAbstract:Abstract The PKR Protein kinase is among the best-studied effectors of the host interferon (IFN)-induced antiviral and antiproliferative response system. In response to stress signals, including virus infection, the normally latent PKR becomes activated through autophosphorylation and dimerization and phosphorylates the eIF2α translation initiation factor subunit, leading to an inhibition of mRNA translation initiation. While numerous virally encoded or modulated Proteins that bind and inhibit PKR during virus infection have been studied, little is known about the cellular Proteins that counteract PKR activity in uninfected cells. Overexpression of PKR in yeast also leads to an inhibition of eIF2α-dependent Protein synthesis, resulting in severe growth suppression. Screening of a human cDNA library for clones capable of counteracting the PKR-mediated growth defect in yeast led to the identification of the catalytic subunit (PP1C) of Protein phosphatase 1α. PP1C reduced double-stranded RNA-mediated auto-activation of PKR and inhibited PKR transphosphorylation activities. A specific and direct interaction between PP1C and PKR was detected, with PP1C binding to the N-terminal regulatory region regardless of the double-stranded RNA-binding activity of PKR. Importantly, a consensus motif shared by many PP1C-interacting Proteins was necessary for PKR binding to PP1C. The PKR-interactive site was mapped to a C-terminal non-catalytic region that is conserved in the PP1C2 isoform. Indeed, co-expression of PP1C or PP1C2 inhibited PKR dimer formation in Escherichia coli. Interestingly, co-expression of a PP1C mutant lacking the catalytic domain, despite retaining its ability to bind PKR, did not prevent PKR dimerization. Our findings suggest that PP1Cmodulates PKR activity via Protein Dephosphorylation and subsequent disruption of PKR dimers.
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the direct binding of the catalytic subunit of Protein phosphatase 1 to the pkr Protein kinase is necessary but not sufficient for inactivation and disruption of enzyme dimer formation
2002Co-Authors: Semih U Tareen, Mark W Melville, Collin M Blakely, Michael G KatzeAbstract:Abstract The PKR Protein kinase is among the best-studied effectors of the host interferon (IFN)-induced antiviral and antiproliferative response system. In response to stress signals, including virus infection, the normally latent PKR becomes activated through autophosphorylation and dimerization and phosphorylates the eIF2α translation initiation factor subunit, leading to an inhibition of mRNA translation initiation. While numerous virally encoded or modulated Proteins that bind and inhibit PKR during virus infection have been studied, little is known about the cellular Proteins that counteract PKR activity in uninfected cells. Overexpression of PKR in yeast also leads to an inhibition of eIF2α-dependent Protein synthesis, resulting in severe growth suppression. Screening of a human cDNA library for clones capable of counteracting the PKR-mediated growth defect in yeast led to the identification of the catalytic subunit (PP1C) of Protein phosphatase 1α. PP1C reduced double-stranded RNA-mediated auto-activation of PKR and inhibited PKR transphosphorylation activities. A specific and direct interaction between PP1C and PKR was detected, with PP1C binding to the N-terminal regulatory region regardless of the double-stranded RNA-binding activity of PKR. Importantly, a consensus motif shared by many PP1C-interacting Proteins was necessary for PKR binding to PP1C. The PKR-interactive site was mapped to a C-terminal non-catalytic region that is conserved in the PP1C2 isoform. Indeed, co-expression of PP1C or PP1C2 inhibited PKR dimer formation in Escherichia coli. Interestingly, co-expression of a PP1C mutant lacking the catalytic domain, despite retaining its ability to bind PKR, did not prevent PKR dimerization. Our findings suggest that PP1Cmodulates PKR activity via Protein Dephosphorylation and subsequent disruption of PKR dimers.
Ruth W Craig - One of the best experts on this subject based on the ideXlab platform.
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inhibition of Protein phosphatase 2a pp2a prevents mcl 1 Protein Dephosphorylation at the thr 163 ser 159 phosphodegron dramatically reducing expression in mcl 1 amplified lymphoma cells
2014Co-Authors: Shanna K Nifoussi, Nora R Ratcliffe, Deborah L Ornstein, Gary Kasof, Stefan Strack, Ruth W CraigAbstract:Abundant, sustained expression of prosurvival Mcl-1 is an important determinant of viability and drug resistance in cancer cells. The Mcl-1 Protein contains PEST sequences (enriched in proline, glutamic acid, serine, and threonine) and is normally subject to rapid turnover via multiple different pathways. One of these pathways involves a phosphodegron in the PEST region, where Thr-163 phosphorylation primes for Ser-159 phosphorylation by glycogen synthase kinase-3. Turnover via this phosphodegron-targeted pathway is reduced in Mcl-1-overexpressing BL41-3 Burkitt lymphoma and other cancer cells; turnover is further slowed in the presence of phorbol ester-induced ERK activation, resulting in Mcl-1 stabilization and an exacerbation of chemoresistance. The present studies focused on Mcl-1 Dephosphorylation, which was also found to profoundly influence turnover. Exposure of BL41-3 cells to an inhibitor of Protein phosphatase 2A (PP2A), okadaic acid, resulted in a rapid increase in phosphorylation at Thr-163 and Ser-159, along with a precipitous decrease in Mcl-1 expression. The decline in Mcl-1 expression preceded the appearance of cell death markers and was not slowed in the presence of phorbol ester. Upon exposure to calyculin A, which also potently inhibits PP2A, versus tautomycin, which does not, only the former increased Thr-163/Ser-159 phosphorylation and decreased Mcl-1 expression. Mcl-1 co-immunoprecipitated with PP2A upon transfection into CHO cells, and PP2A/Aα knockdown recapitulated the increase in Mcl-1 phosphorylation and decrease in expression. In sum, inhibition of PP2A prevents Mcl-1 Dephosphorylation and results in rapid loss of this prosurvival Protein in chemoresistant cancer cells.
Semih U Tareen - One of the best experts on this subject based on the ideXlab platform.
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the direct binding of the catalytic subunit of Protein phosphatase 1 to the pkr Protein kinase is necessary but not sufficient for inactivation and disruption of enzyme dimer formation
2002Co-Authors: Seng Lai Tan, Semih U Tareen, Mark W Melville, Collin M Blakely, Michael G KatzeAbstract:Abstract The PKR Protein kinase is among the best-studied effectors of the host interferon (IFN)-induced antiviral and antiproliferative response system. In response to stress signals, including virus infection, the normally latent PKR becomes activated through autophosphorylation and dimerization and phosphorylates the eIF2α translation initiation factor subunit, leading to an inhibition of mRNA translation initiation. While numerous virally encoded or modulated Proteins that bind and inhibit PKR during virus infection have been studied, little is known about the cellular Proteins that counteract PKR activity in uninfected cells. Overexpression of PKR in yeast also leads to an inhibition of eIF2α-dependent Protein synthesis, resulting in severe growth suppression. Screening of a human cDNA library for clones capable of counteracting the PKR-mediated growth defect in yeast led to the identification of the catalytic subunit (PP1C) of Protein phosphatase 1α. PP1C reduced double-stranded RNA-mediated auto-activation of PKR and inhibited PKR transphosphorylation activities. A specific and direct interaction between PP1C and PKR was detected, with PP1C binding to the N-terminal regulatory region regardless of the double-stranded RNA-binding activity of PKR. Importantly, a consensus motif shared by many PP1C-interacting Proteins was necessary for PKR binding to PP1C. The PKR-interactive site was mapped to a C-terminal non-catalytic region that is conserved in the PP1C2 isoform. Indeed, co-expression of PP1C or PP1C2 inhibited PKR dimer formation in Escherichia coli. Interestingly, co-expression of a PP1C mutant lacking the catalytic domain, despite retaining its ability to bind PKR, did not prevent PKR dimerization. Our findings suggest that PP1Cmodulates PKR activity via Protein Dephosphorylation and subsequent disruption of PKR dimers.
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the direct binding of the catalytic subunit of Protein phosphatase 1 to the pkr Protein kinase is necessary but not sufficient for inactivation and disruption of enzyme dimer formation
2002Co-Authors: Semih U Tareen, Mark W Melville, Collin M Blakely, Michael G KatzeAbstract:Abstract The PKR Protein kinase is among the best-studied effectors of the host interferon (IFN)-induced antiviral and antiproliferative response system. In response to stress signals, including virus infection, the normally latent PKR becomes activated through autophosphorylation and dimerization and phosphorylates the eIF2α translation initiation factor subunit, leading to an inhibition of mRNA translation initiation. While numerous virally encoded or modulated Proteins that bind and inhibit PKR during virus infection have been studied, little is known about the cellular Proteins that counteract PKR activity in uninfected cells. Overexpression of PKR in yeast also leads to an inhibition of eIF2α-dependent Protein synthesis, resulting in severe growth suppression. Screening of a human cDNA library for clones capable of counteracting the PKR-mediated growth defect in yeast led to the identification of the catalytic subunit (PP1C) of Protein phosphatase 1α. PP1C reduced double-stranded RNA-mediated auto-activation of PKR and inhibited PKR transphosphorylation activities. A specific and direct interaction between PP1C and PKR was detected, with PP1C binding to the N-terminal regulatory region regardless of the double-stranded RNA-binding activity of PKR. Importantly, a consensus motif shared by many PP1C-interacting Proteins was necessary for PKR binding to PP1C. The PKR-interactive site was mapped to a C-terminal non-catalytic region that is conserved in the PP1C2 isoform. Indeed, co-expression of PP1C or PP1C2 inhibited PKR dimer formation in Escherichia coli. Interestingly, co-expression of a PP1C mutant lacking the catalytic domain, despite retaining its ability to bind PKR, did not prevent PKR dimerization. Our findings suggest that PP1Cmodulates PKR activity via Protein Dephosphorylation and subsequent disruption of PKR dimers.