Severe acute respiratory syndrome-associated coronavirus nucleocapsid protein interacts with Smad3 and modulates transforming growth factor-beta signaling.
Identifieur interne : 003087 ( Main/Merge ); précédent : 003086; suivant : 003088Severe acute respiratory syndrome-associated coronavirus nucleocapsid protein interacts with Smad3 and modulates transforming growth factor-beta signaling.
Auteurs : Xingang Zhao [République populaire de Chine] ; John M. Nicholls ; Ye-Guang ChenSource :
- The Journal of biological chemistry [ 0021-9258 ] ; 2008.
Descripteurs français
- KwdFr :
- Animaux, Apoptose, Facteur de croissance transformant bêta (métabolisme), Fibrose (anatomopathologie), Humains, Liaison aux protéines, Lignée cellulaire, Protéine Smad-3 (métabolisme), Protéine Smad-4 (métabolisme), Protéines nucléocapside (métabolisme), Régulation de l'expression des gènes viraux, Souris, Structure tertiaire des protéines, Transduction du signal, Virus du SRAS (métabolisme).
- MESH :
- anatomopathologie : Fibrose.
- métabolisme : Facteur de croissance transformant bêta, Protéine Smad-3, Protéine Smad-4, Protéines nucléocapside, Virus du SRAS.
- Animaux, Apoptose, Humains, Liaison aux protéines, Lignée cellulaire, Régulation de l'expression des gènes viraux, Souris, Structure tertiaire des protéines, Transduction du signal.
English descriptors
- KwdEn :
- Animals, Apoptosis, Cell Line, Fibrosis (pathology), Gene Expression Regulation, Viral, Humans, Mice, Nucleocapsid Proteins (metabolism), Protein Binding, Protein Structure, Tertiary, SARS Virus (metabolism), Signal Transduction, Smad3 Protein (metabolism), Smad4 Protein (metabolism), Transforming Growth Factor beta (metabolism).
- MESH :
- chemical , metabolism : Nucleocapsid Proteins, Smad3 Protein, Smad4 Protein, Transforming Growth Factor beta.
- metabolism : SARS Virus.
- pathology : Fibrosis.
- Animals, Apoptosis, Cell Line, Gene Expression Regulation, Viral, Humans, Mice, Protein Binding, Protein Structure, Tertiary, Signal Transduction.
Abstract
Severe acute respiratory syndrome (SARS) is an acute infectious disease with significant mortality. A typical clinical feature associated with SARS is pulmonary fibrosis and the associated lung failure. However, the underlying mechanism remains elusive. In this study, we demonstrate that SARS-associated coronavirus (SARS-CoV) nucleocapsid (N) protein potentiates transforming growth factor-beta (TGF-beta)-induced expression of plasminogen activator inhibitor-1 but attenuates Smad3/Smad4-mediated apoptosis of human peripheral lung epithelial HPL1 cells. The promoting effect of N protein on the transcriptional responses of TGF-beta is Smad3-specific. N protein associates with Smad3 and promotes Smad3-p300 complex formation while it interferes with the complex formation between Smad3 and Smad4. These findings provide evidence of a novel mechanism whereby N protein modulates TGF-beta signaling to block apoptosis of SARS-CoV-infected host cells and meanwhile promote tissue fibrosis. Our results reveal a novel mode of Smad3 action in a Smad4-independent manner and may lead to successful strategies for SARS treatment by targeting the TGF-beta signaling molecules.
DOI: 10.1074/jbc.M708033200
PubMed: 18055455
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pubmed:18055455Le document en format XML
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<term>Apoptosis</term>
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<term>Gene Expression Regulation, Viral</term>
<term>Humans</term>
<term>Mice</term>
<term>Nucleocapsid Proteins (metabolism)</term>
<term>Protein Binding</term>
<term>Protein Structure, Tertiary</term>
<term>SARS Virus (metabolism)</term>
<term>Signal Transduction</term>
<term>Smad3 Protein (metabolism)</term>
<term>Smad4 Protein (metabolism)</term>
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<term>Apoptose</term>
<term>Facteur de croissance transformant bêta (métabolisme)</term>
<term>Fibrose (anatomopathologie)</term>
<term>Humains</term>
<term>Liaison aux protéines</term>
<term>Lignée cellulaire</term>
<term>Protéine Smad-3 (métabolisme)</term>
<term>Protéine Smad-4 (métabolisme)</term>
<term>Protéines nucléocapside (métabolisme)</term>
<term>Régulation de l'expression des gènes viraux</term>
<term>Souris</term>
<term>Structure tertiaire des protéines</term>
<term>Transduction du signal</term>
<term>Virus du SRAS (métabolisme)</term>
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<keywords scheme="MESH" type="chemical" qualifier="metabolism" xml:lang="en"><term>Nucleocapsid Proteins</term>
<term>Smad3 Protein</term>
<term>Smad4 Protein</term>
<term>Transforming Growth Factor beta</term>
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<keywords scheme="MESH" qualifier="anatomopathologie" xml:lang="fr"><term>Fibrose</term>
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<keywords scheme="MESH" qualifier="métabolisme" xml:lang="fr"><term>Facteur de croissance transformant bêta</term>
<term>Protéine Smad-3</term>
<term>Protéine Smad-4</term>
<term>Protéines nucléocapside</term>
<term>Virus du SRAS</term>
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<keywords scheme="MESH" qualifier="pathology" xml:lang="en"><term>Fibrosis</term>
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<term>Apoptosis</term>
<term>Cell Line</term>
<term>Gene Expression Regulation, Viral</term>
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<term>Mice</term>
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<term>Protein Structure, Tertiary</term>
<term>Signal Transduction</term>
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<term>Apoptose</term>
<term>Humains</term>
<term>Liaison aux protéines</term>
<term>Lignée cellulaire</term>
<term>Régulation de l'expression des gènes viraux</term>
<term>Souris</term>
<term>Structure tertiaire des protéines</term>
<term>Transduction du signal</term>
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<front><div type="abstract" xml:lang="en">Severe acute respiratory syndrome (SARS) is an acute infectious disease with significant mortality. A typical clinical feature associated with SARS is pulmonary fibrosis and the associated lung failure. However, the underlying mechanism remains elusive. In this study, we demonstrate that SARS-associated coronavirus (SARS-CoV) nucleocapsid (N) protein potentiates transforming growth factor-beta (TGF-beta)-induced expression of plasminogen activator inhibitor-1 but attenuates Smad3/Smad4-mediated apoptosis of human peripheral lung epithelial HPL1 cells. The promoting effect of N protein on the transcriptional responses of TGF-beta is Smad3-specific. N protein associates with Smad3 and promotes Smad3-p300 complex formation while it interferes with the complex formation between Smad3 and Smad4. These findings provide evidence of a novel mechanism whereby N protein modulates TGF-beta signaling to block apoptosis of SARS-CoV-infected host cells and meanwhile promote tissue fibrosis. Our results reveal a novel mode of Smad3 action in a Smad4-independent manner and may lead to successful strategies for SARS treatment by targeting the TGF-beta signaling molecules.</div>
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