The coronavirus endoribonuclease Nsp15 interacts with retinoblastoma tumor suppressor protein.
Identifieur interne : 001C38 ( Main/Exploration ); précédent : 001C37; suivant : 001C39The coronavirus endoribonuclease Nsp15 interacts with retinoblastoma tumor suppressor protein.
Auteurs : Kanchan Bhardwaj [États-Unis] ; Pinghua Liu ; Julian L. Leibowitz ; C Cheng KaoSource :
- Journal of virology [ 1098-5514 ] ; 2012.
Descripteurs français
- KwdFr :
- Animaux, Apoptose (génétique), Cricetinae, Endoribonucleases (génétique), Endoribonucleases (métabolisme), Humains, Infections à coronavirus (métabolisme), Liaison aux protéines, Lignée cellulaire, Modèles moléculaires, Motifs d'acides aminés, Motifs et domaines d'intéraction protéique, Mutation, Protéine du rétinoblastome (génétique), Protéine du rétinoblastome (métabolisme), Protéines virales non structurales (), Protéines virales non structurales (génétique), Protéines virales non structurales (métabolisme), Régulation de l'expression des gènes, Sites de fixation, Souris, Séquence d'acides aminés, Transport de protéines, Virus de l'hépatite murine (enzymologie), Virus de l'hépatite murine (génétique).
- MESH :
- enzymologie : Virus de l'hépatite murine.
- génétique : Apoptose, Endoribonucleases, Protéine du rétinoblastome, Protéines virales non structurales, Virus de l'hépatite murine.
- métabolisme : Endoribonucleases, Infections à coronavirus, Protéine du rétinoblastome, Protéines virales non structurales.
- Animaux, Cricetinae, Humains, Liaison aux protéines, Lignée cellulaire, Modèles moléculaires, Motifs d'acides aminés, Motifs et domaines d'intéraction protéique, Mutation, Protéines virales non structurales, Régulation de l'expression des gènes, Sites de fixation, Souris, Séquence d'acides aminés, Transport de protéines.
English descriptors
- KwdEn :
- Amino Acid Motifs, Amino Acid Sequence, Animals, Apoptosis (genetics), Binding Sites, Cell Line, Coronavirus Infections (metabolism), Cricetinae, Endoribonucleases (genetics), Endoribonucleases (metabolism), Gene Expression Regulation, Humans, Mice, Models, Molecular, Murine hepatitis virus (enzymology), Murine hepatitis virus (genetics), Mutation, Protein Binding, Protein Interaction Domains and Motifs, Protein Transport, Retinoblastoma Protein (genetics), Retinoblastoma Protein (metabolism), Viral Nonstructural Proteins (chemistry), Viral Nonstructural Proteins (genetics), Viral Nonstructural Proteins (metabolism).
- MESH :
- chemical , chemistry : Viral Nonstructural Proteins.
- chemical , genetics : Endoribonucleases, Retinoblastoma Protein, Viral Nonstructural Proteins.
- enzymology : Murine hepatitis virus.
- genetics : Apoptosis, Murine hepatitis virus.
- metabolism : Coronavirus Infections, Endoribonucleases, Retinoblastoma Protein, Viral Nonstructural Proteins.
- Amino Acid Motifs, Amino Acid Sequence, Animals, Binding Sites, Cell Line, Cricetinae, Gene Expression Regulation, Humans, Mice, Models, Molecular, Mutation, Protein Binding, Protein Interaction Domains and Motifs, Protein Transport.
Abstract
Coronaviruses encode an endoribonuclease, Nsp15, which has a poorly defined role in infection. Sequence analysis revealed a retinoblastoma protein-binding motif (LXCXE/D) in the majority of the Nsp15 of the severe acute respiratory syndrome coronavirus (SARS-CoV) and its orthologs in the alpha and beta coronaviruses. The endoribonuclease activity of the SARS-CoV Nsp15 (sNsp15) was stimulated by retinoblastoma protein (pRb) in vitro, and the two proteins can be coimmunoprecipitated from cellular extracts. Mutations in the pRb-binding motif rendered sNsp15 to be differentially modified by ubiquitin in cells, and cytotoxicity was observed upon its expression. Expression of the sNsp15 in cells resulted in an increased abundance of pRb in the cytoplasm, decreased overall levels of pRb, an increased proportion of cells in the S phase of the cell cycle, and an enhanced expression from a promoter normally repressed by pRb. The endoribonuclease activity of the mouse hepatitis virus (MHV) A59 Nsp15 was also increased by pRb in vitro, and an MHV with mutations in the LXCXE/D-motif, named vLC, exhibited a smaller plaque diameter and reduced the virus titer by ∼1 log. Overexpression of pRb delayed the viral protein production by wild-type MHV but not by vLC. This study reveals that pRb and its interaction with Nsp15 can affect coronavirus infection and adds coronaviruses to a small but growing family of RNA viruses that encode a protein to interact with pRb.
DOI: 10.1128/JVI.07012-11
PubMed: 22301153
Affiliations:
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Le document en format XML
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Leibowitz</name></author><author><name sortKey="Kao, C Cheng" sort="Kao, C Cheng" uniqKey="Kao C" first="C Cheng" last="Kao">C Cheng Kao</name></author></analytic><series><title level="j">Journal of virology</title><idno type="eISSN">1098-5514</idno><imprint><date when="2012" type="published">2012</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Amino Acid Motifs</term><term>Amino Acid Sequence</term><term>Animals</term><term>Apoptosis (genetics)</term><term>Binding Sites</term><term>Cell Line</term><term>Coronavirus Infections (metabolism)</term><term>Cricetinae</term><term>Endoribonucleases (genetics)</term><term>Endoribonucleases (metabolism)</term><term>Gene Expression Regulation</term><term>Humans</term><term>Mice</term><term>Models, Molecular</term><term>Murine hepatitis virus (enzymology)</term><term>Murine hepatitis virus (genetics)</term><term>Mutation</term><term>Protein Binding</term><term>Protein Interaction Domains and Motifs</term><term>Protein Transport</term><term>Retinoblastoma Protein (genetics)</term><term>Retinoblastoma Protein (metabolism)</term><term>Viral Nonstructural Proteins (chemistry)</term><term>Viral Nonstructural Proteins (genetics)</term><term>Viral Nonstructural Proteins (metabolism)</term></keywords><keywords scheme="KwdFr" xml:lang="fr"><term>Animaux</term><term>Apoptose (génétique)</term><term>Cricetinae</term><term>Endoribonucleases (génétique)</term><term>Endoribonucleases (métabolisme)</term><term>Humains</term><term>Infections à coronavirus (métabolisme)</term><term>Liaison aux protéines</term><term>Lignée cellulaire</term><term>Modèles moléculaires</term><term>Motifs d'acides aminés</term><term>Motifs et domaines d'intéraction protéique</term><term>Mutation</term><term>Protéine du rétinoblastome (génétique)</term><term>Protéine du rétinoblastome (métabolisme)</term><term>Protéines virales non structurales ()</term><term>Protéines virales non structurales (génétique)</term><term>Protéines virales non structurales (métabolisme)</term><term>Régulation de l'expression des gènes</term><term>Sites de fixation</term><term>Souris</term><term>Séquence d'acides aminés</term><term>Transport de protéines</term><term>Virus de l'hépatite murine (enzymologie)</term><term>Virus de l'hépatite murine (génétique)</term></keywords><keywords scheme="MESH" type="chemical" qualifier="chemistry" xml:lang="en"><term>Viral Nonstructural Proteins</term></keywords><keywords scheme="MESH" type="chemical" qualifier="genetics" xml:lang="en"><term>Endoribonucleases</term><term>Retinoblastoma Protein</term><term>Viral Nonstructural Proteins</term></keywords><keywords scheme="MESH" qualifier="enzymologie" xml:lang="fr"><term>Virus de l'hépatite murine</term></keywords><keywords scheme="MESH" qualifier="enzymology" xml:lang="en"><term>Murine hepatitis virus</term></keywords><keywords scheme="MESH" qualifier="genetics" xml:lang="en"><term>Apoptosis</term><term>Murine hepatitis virus</term></keywords><keywords scheme="MESH" qualifier="génétique" xml:lang="fr"><term>Apoptose</term><term>Endoribonucleases</term><term>Protéine du rétinoblastome</term><term>Protéines virales non structurales</term><term>Virus de l'hépatite murine</term></keywords><keywords scheme="MESH" qualifier="metabolism" xml:lang="en"><term>Coronavirus Infections</term><term>Endoribonucleases</term><term>Retinoblastoma Protein</term><term>Viral Nonstructural Proteins</term></keywords><keywords scheme="MESH" qualifier="métabolisme" xml:lang="fr"><term>Endoribonucleases</term><term>Infections à coronavirus</term><term>Protéine du rétinoblastome</term><term>Protéines virales non structurales</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Amino Acid Motifs</term><term>Amino Acid Sequence</term><term>Animals</term><term>Binding Sites</term><term>Cell Line</term><term>Cricetinae</term><term>Gene Expression Regulation</term><term>Humans</term><term>Mice</term><term>Models, Molecular</term><term>Mutation</term><term>Protein Binding</term><term>Protein Interaction Domains and Motifs</term><term>Protein Transport</term></keywords><keywords scheme="MESH" xml:lang="fr"><term>Animaux</term><term>Cricetinae</term><term>Humains</term><term>Liaison aux protéines</term><term>Lignée cellulaire</term><term>Modèles moléculaires</term><term>Motifs d'acides aminés</term><term>Motifs et domaines d'intéraction protéique</term><term>Mutation</term><term>Protéines virales non structurales</term><term>Régulation de l'expression des gènes</term><term>Sites de fixation</term><term>Souris</term><term>Séquence d'acides aminés</term><term>Transport de protéines</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">Coronaviruses encode an endoribonuclease, Nsp15, which has a poorly defined role in infection. Sequence analysis revealed a retinoblastoma protein-binding motif (LXCXE/D) in the majority of the Nsp15 of the severe acute respiratory syndrome coronavirus (SARS-CoV) and its orthologs in the alpha and beta coronaviruses. The endoribonuclease activity of the SARS-CoV Nsp15 (sNsp15) was stimulated by retinoblastoma protein (pRb) in vitro, and the two proteins can be coimmunoprecipitated from cellular extracts. Mutations in the pRb-binding motif rendered sNsp15 to be differentially modified by ubiquitin in cells, and cytotoxicity was observed upon its expression. Expression of the sNsp15 in cells resulted in an increased abundance of pRb in the cytoplasm, decreased overall levels of pRb, an increased proportion of cells in the S phase of the cell cycle, and an enhanced expression from a promoter normally repressed by pRb. The endoribonuclease activity of the mouse hepatitis virus (MHV) A59 Nsp15 was also increased by pRb in vitro, and an MHV with mutations in the LXCXE/D-motif, named vLC, exhibited a smaller plaque diameter and reduced the virus titer by ∼1 log. Overexpression of pRb delayed the viral protein production by wild-type MHV but not by vLC. This study reveals that pRb and its interaction with Nsp15 can affect coronavirus infection and adds coronaviruses to a small but growing family of RNA viruses that encode a protein to interact with pRb.</div></front></TEI><affiliations><list><country><li>États-Unis</li></country><region><li>Indiana</li></region></list><tree><noCountry><name sortKey="Kao, C Cheng" sort="Kao, C Cheng" uniqKey="Kao C" first="C Cheng" last="Kao">C Cheng Kao</name><name sortKey="Leibowitz, Julian L" sort="Leibowitz, Julian L" uniqKey="Leibowitz J" first="Julian L" last="Leibowitz">Julian L. Leibowitz</name><name sortKey="Liu, Pinghua" sort="Liu, Pinghua" uniqKey="Liu P" first="Pinghua" last="Liu">Pinghua Liu</name></noCountry><country name="États-Unis"><region name="Indiana"><name sortKey="Bhardwaj, Kanchan" sort="Bhardwaj, Kanchan" uniqKey="Bhardwaj K" first="Kanchan" last="Bhardwaj">Kanchan Bhardwaj</name></region></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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