SARS coronavirus 7a protein blocks cell cycle progression at G0/G1 phase via the cyclin D3/pRb pathway.
Identifieur interne : 003D36 ( Main/Exploration ); précédent : 003D35; suivant : 003D37SARS coronavirus 7a protein blocks cell cycle progression at G0/G1 phase via the cyclin D3/pRb pathway.
Auteurs : Xiaoling Yuan [République populaire de Chine] ; Jie Wu ; Yajun Shan ; Zhenyu Yao ; Bo Dong ; Bo Chen ; Zhenhu Zhao ; Shenqi Wang ; Jiapei Chen ; Yuwen CongSource :
- Virology [ 0042-6822 ] ; 2006.
Descripteurs français
- KwdFr :
- ARN messager (génétique), ARN messager (métabolisme), Animaux, Cellules COS, Cellules Vero, Cycline D3, Cyclines (génétique), Cyclines (métabolisme), Humains, Lignée cellulaire, Mutation, Phase G0, Phase G1, Phosphorylation, Protéine du rétinoblastome (génétique), Protéine du rétinoblastome (métabolisme), Protéines de la matrice virale, Protéines membranaires (), Protéines membranaires (génétique), Protéines membranaires (métabolisme), Protéines virales (), Protéines virales (génétique), Protéines virales (métabolisme), Régulation de l'expression des gènes, Transcription génétique, Transfection, Virus du SRAS (pathogénicité), Virus du SRAS (physiologie).
- MESH :
- génétique : ARN messager, Cyclines, Protéine du rétinoblastome, Protéines membranaires, Protéines virales.
- métabolisme : ARN messager, Cyclines, Protéine du rétinoblastome, Protéines membranaires, Protéines virales.
- pathogénicité : Virus du SRAS.
- physiologie : Virus du SRAS.
- Animaux, Cellules COS, Cellules Vero, Cycline D3, Humains, Lignée cellulaire, Mutation, Phase G0, Phase G1, Phosphorylation, Protéines de la matrice virale, Protéines membranaires, Protéines virales, Régulation de l'expression des gènes, Transcription génétique, Transfection.
English descriptors
- KwdEn :
- Animals, COS Cells, Cell Line, Chlorocebus aethiops, Cyclin D3, Cyclins (genetics), Cyclins (metabolism), G1 Phase, Gene Expression Regulation, Humans, Membrane Proteins (chemistry), Membrane Proteins (genetics), Membrane Proteins (metabolism), Mutation, Phosphorylation, RNA, Messenger (genetics), RNA, Messenger (metabolism), Resting Phase, Cell Cycle, Retinoblastoma Protein (genetics), Retinoblastoma Protein (metabolism), SARS Virus (pathogenicity), SARS Virus (physiology), Transcription, Genetic, Transfection, Vero Cells, Viral Matrix Proteins, Viral Proteins (chemistry), Viral Proteins (genetics), Viral Proteins (metabolism).
- MESH :
- chemical , chemistry : Membrane Proteins, Viral Proteins.
- chemical , genetics : Cyclins, Membrane Proteins, RNA, Messenger, Retinoblastoma Protein, Viral Proteins.
- chemical , metabolism : Cyclins, Membrane Proteins, RNA, Messenger, Retinoblastoma Protein, Viral Proteins.
- chemical : Cyclin D3, Viral Matrix Proteins.
- pathogenicity : SARS Virus.
- physiology : SARS Virus.
- Animals, COS Cells, Cell Line, Chlorocebus aethiops, G1 Phase, Gene Expression Regulation, Humans, Mutation, Phosphorylation, Resting Phase, Cell Cycle, Transcription, Genetic, Transfection, Vero Cells.
Abstract
The genome of severe acute respiratory syndrome-associated coronavirus (SARS-CoV) contains four structural genes that are homologous to genes found in other coronaviruses, and also contains six subgroup-specific open reading frames (ORFs). Expression of one of these subgroup-specific genes, ORF7a, resulted in apoptosis via a caspase-dependent pathway. Here, we observed that transient expression of ORF7a protein fused with myc or GFP tags at its N or C terminus inhibited cell growth and prevented BrdU incorporation in different cultural cells, suggesting that ORF7a expression may regulate cell cycle progression. Analysis by flow cytometry demonstrated that ORF7a expression was associated with blockage of cell cycle progression at G0/G1 phase in HEK 293 cells after 24 to 60 h post-transfection. Similar results were observed in COS-7 and Vero cells. Mutation analysis of ORF7a revealed that the domain spanning aa 44-82 of 7a protein was essential for its cytoplasmic localization and for induction of the cell cycle arrest. After analyzing the cellular proteins involving in regulation of cell cycle progression, we demonstrated that ORF7a expression was correlated with a significant reduction of cyclin D3 level of mRNA transcription and expression, and phosphorylation of retinoblastoma (Rb) protein at ser795 and ser809/811, not with the expression of cyclin D1, D2, cdk4 and cdk6 in HEK 293 cells. These results suggest that the insufficient expression of cyclin D3 may cause a decreased activity of cyclin D/cdk4/6, resulting in the inhibition of Rb phosphorylation. Accumulation of hypo- or non-phosphorylated pRb thus prevents cell cycle progression at G0/G1 phase.
DOI: 10.1016/j.virol.2005.10.015
PubMed: 16303160
Affiliations:
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Shan</name></author><author><name sortKey="Yao, Zhenyu" sort="Yao, Zhenyu" uniqKey="Yao Z" first="Zhenyu" last="Yao">Zhenyu Yao</name></author><author><name sortKey="Dong, Bo" sort="Dong, Bo" uniqKey="Dong B" first="Bo" last="Dong">Bo Dong</name></author><author><name sortKey="Chen, Bo" sort="Chen, Bo" uniqKey="Chen B" first="Bo" last="Chen">Bo Chen</name></author><author><name sortKey="Zhao, Zhenhu" sort="Zhao, Zhenhu" uniqKey="Zhao Z" first="Zhenhu" last="Zhao">Zhenhu Zhao</name></author><author><name sortKey="Wang, Shenqi" sort="Wang, Shenqi" uniqKey="Wang S" first="Shenqi" last="Wang">Shenqi Wang</name></author><author><name sortKey="Chen, Jiapei" sort="Chen, Jiapei" uniqKey="Chen J" first="Jiapei" last="Chen">Jiapei Chen</name></author><author><name sortKey="Cong, Yuwen" sort="Cong, Yuwen" uniqKey="Cong Y" first="Yuwen" last="Cong">Yuwen Cong</name></author></titleStmt><publicationStmt><idno type="wicri:source">PubMed</idno><date when="2006">2006</date><idno 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xml:lang="en">SARS coronavirus 7a protein blocks cell cycle progression at G0/G1 phase via the cyclin D3/pRb pathway.</title><author><name sortKey="Yuan, Xiaoling" sort="Yuan, Xiaoling" uniqKey="Yuan X" first="Xiaoling" last="Yuan">Xiaoling Yuan</name><affiliation wicri:level="1"><nlm:affiliation>Department of Pathophysiology, Beijing Institute of Radiation Medicine, No. 27 Taiping Road, Beijing 100850, China.</nlm:affiliation><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Department of Pathophysiology, Beijing Institute of Radiation Medicine, No. 27 Taiping Road, Beijing 100850</wicri:regionArea><placeName><settlement type="city">Pékin</settlement></placeName></affiliation></author><author><name sortKey="Wu, Jie" sort="Wu, Jie" uniqKey="Wu J" first="Jie" last="Wu">Jie Wu</name></author><author><name sortKey="Shan, Yajun" sort="Shan, Yajun" uniqKey="Shan Y" first="Yajun" last="Shan">Yajun Shan</name></author><author><name sortKey="Yao, Zhenyu" sort="Yao, Zhenyu" uniqKey="Yao Z" first="Zhenyu" last="Yao">Zhenyu Yao</name></author><author><name sortKey="Dong, Bo" sort="Dong, Bo" uniqKey="Dong B" first="Bo" last="Dong">Bo Dong</name></author><author><name sortKey="Chen, Bo" sort="Chen, Bo" uniqKey="Chen B" first="Bo" last="Chen">Bo Chen</name></author><author><name sortKey="Zhao, Zhenhu" sort="Zhao, Zhenhu" uniqKey="Zhao Z" first="Zhenhu" last="Zhao">Zhenhu Zhao</name></author><author><name sortKey="Wang, Shenqi" sort="Wang, Shenqi" uniqKey="Wang S" first="Shenqi" last="Wang">Shenqi Wang</name></author><author><name sortKey="Chen, Jiapei" sort="Chen, Jiapei" uniqKey="Chen J" first="Jiapei" last="Chen">Jiapei Chen</name></author><author><name sortKey="Cong, Yuwen" sort="Cong, Yuwen" uniqKey="Cong Y" first="Yuwen" last="Cong">Yuwen Cong</name></author></analytic><series><title level="j">Virology</title><idno type="ISSN">0042-6822</idno><imprint><date when="2006" type="published">2006</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Animals</term><term>COS Cells</term><term>Cell Line</term><term>Chlorocebus aethiops</term><term>Cyclin D3</term><term>Cyclins (genetics)</term><term>Cyclins (metabolism)</term><term>G1 Phase</term><term>Gene Expression Regulation</term><term>Humans</term><term>Membrane Proteins (chemistry)</term><term>Membrane Proteins (genetics)</term><term>Membrane Proteins (metabolism)</term><term>Mutation</term><term>Phosphorylation</term><term>RNA, Messenger (genetics)</term><term>RNA, Messenger (metabolism)</term><term>Resting Phase, Cell Cycle</term><term>Retinoblastoma Protein (genetics)</term><term>Retinoblastoma Protein (metabolism)</term><term>SARS Virus (pathogenicity)</term><term>SARS Virus (physiology)</term><term>Transcription, Genetic</term><term>Transfection</term><term>Vero Cells</term><term>Viral Matrix Proteins</term><term>Viral Proteins (chemistry)</term><term>Viral Proteins (genetics)</term><term>Viral Proteins (metabolism)</term></keywords><keywords scheme="KwdFr" xml:lang="fr"><term>ARN messager (génétique)</term><term>ARN messager (métabolisme)</term><term>Animaux</term><term>Cellules COS</term><term>Cellules Vero</term><term>Cycline D3</term><term>Cyclines (génétique)</term><term>Cyclines (métabolisme)</term><term>Humains</term><term>Lignée cellulaire</term><term>Mutation</term><term>Phase G0</term><term>Phase G1</term><term>Phosphorylation</term><term>Protéine du rétinoblastome (génétique)</term><term>Protéine du rétinoblastome (métabolisme)</term><term>Protéines de la matrice virale</term><term>Protéines membranaires ()</term><term>Protéines membranaires (génétique)</term><term>Protéines membranaires (métabolisme)</term><term>Protéines virales ()</term><term>Protéines virales (génétique)</term><term>Protéines virales (métabolisme)</term><term>Régulation de l'expression des gènes</term><term>Transcription génétique</term><term>Transfection</term><term>Virus du SRAS (pathogénicité)</term><term>Virus du SRAS (physiologie)</term></keywords><keywords scheme="MESH" type="chemical" qualifier="chemistry" xml:lang="en"><term>Membrane Proteins</term><term>Viral Proteins</term></keywords><keywords scheme="MESH" type="chemical" qualifier="genetics" xml:lang="en"><term>Cyclins</term><term>Membrane Proteins</term><term>RNA, Messenger</term><term>Retinoblastoma Protein</term><term>Viral Proteins</term></keywords><keywords scheme="MESH" type="chemical" qualifier="metabolism" xml:lang="en"><term>Cyclins</term><term>Membrane Proteins</term><term>RNA, Messenger</term><term>Retinoblastoma Protein</term><term>Viral Proteins</term></keywords><keywords scheme="MESH" type="chemical" xml:lang="en"><term>Cyclin D3</term><term>Viral Matrix Proteins</term></keywords><keywords scheme="MESH" qualifier="génétique" xml:lang="fr"><term>ARN messager</term><term>Cyclines</term><term>Protéine du rétinoblastome</term><term>Protéines membranaires</term><term>Protéines virales</term></keywords><keywords scheme="MESH" qualifier="métabolisme" xml:lang="fr"><term>ARN messager</term><term>Cyclines</term><term>Protéine du rétinoblastome</term><term>Protéines membranaires</term><term>Protéines virales</term></keywords><keywords scheme="MESH" qualifier="pathogenicity" xml:lang="en"><term>SARS Virus</term></keywords><keywords scheme="MESH" qualifier="pathogénicité" xml:lang="fr"><term>Virus du SRAS</term></keywords><keywords scheme="MESH" qualifier="physiologie" xml:lang="fr"><term>Virus du SRAS</term></keywords><keywords scheme="MESH" qualifier="physiology" xml:lang="en"><term>SARS Virus</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Animals</term><term>COS Cells</term><term>Cell Line</term><term>Chlorocebus aethiops</term><term>G1 Phase</term><term>Gene Expression Regulation</term><term>Humans</term><term>Mutation</term><term>Phosphorylation</term><term>Resting Phase, Cell Cycle</term><term>Transcription, Genetic</term><term>Transfection</term><term>Vero Cells</term></keywords><keywords scheme="MESH" xml:lang="fr"><term>Animaux</term><term>Cellules COS</term><term>Cellules Vero</term><term>Cycline D3</term><term>Humains</term><term>Lignée cellulaire</term><term>Mutation</term><term>Phase G0</term><term>Phase G1</term><term>Phosphorylation</term><term>Protéines de la matrice virale</term><term>Protéines membranaires</term><term>Protéines virales</term><term>Régulation de l'expression des gènes</term><term>Transcription génétique</term><term>Transfection</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">The genome of severe acute respiratory syndrome-associated coronavirus (SARS-CoV) contains four structural genes that are homologous to genes found in other coronaviruses, and also contains six subgroup-specific open reading frames (ORFs). Expression of one of these subgroup-specific genes, ORF7a, resulted in apoptosis via a caspase-dependent pathway. Here, we observed that transient expression of ORF7a protein fused with myc or GFP tags at its N or C terminus inhibited cell growth and prevented BrdU incorporation in different cultural cells, suggesting that ORF7a expression may regulate cell cycle progression. Analysis by flow cytometry demonstrated that ORF7a expression was associated with blockage of cell cycle progression at G0/G1 phase in HEK 293 cells after 24 to 60 h post-transfection. Similar results were observed in COS-7 and Vero cells. Mutation analysis of ORF7a revealed that the domain spanning aa 44-82 of 7a protein was essential for its cytoplasmic localization and for induction of the cell cycle arrest. After analyzing the cellular proteins involving in regulation of cell cycle progression, we demonstrated that ORF7a expression was correlated with a significant reduction of cyclin D3 level of mRNA transcription and expression, and phosphorylation of retinoblastoma (Rb) protein at ser795 and ser809/811, not with the expression of cyclin D1, D2, cdk4 and cdk6 in HEK 293 cells. These results suggest that the insufficient expression of cyclin D3 may cause a decreased activity of cyclin D/cdk4/6, resulting in the inhibition of Rb phosphorylation. Accumulation of hypo- or non-phosphorylated pRb thus prevents cell cycle progression at G0/G1 phase.</div></front></TEI><affiliations><list><country><li>République populaire de Chine</li></country><settlement><li>Pékin</li></settlement></list><tree><noCountry><name sortKey="Chen, Bo" sort="Chen, Bo" uniqKey="Chen B" first="Bo" last="Chen">Bo Chen</name><name sortKey="Chen, Jiapei" sort="Chen, Jiapei" uniqKey="Chen J" first="Jiapei" last="Chen">Jiapei Chen</name><name sortKey="Cong, Yuwen" sort="Cong, Yuwen" uniqKey="Cong Y" first="Yuwen" last="Cong">Yuwen Cong</name><name sortKey="Dong, Bo" sort="Dong, Bo" uniqKey="Dong B" first="Bo" last="Dong">Bo Dong</name><name sortKey="Shan, Yajun" sort="Shan, Yajun" uniqKey="Shan Y" first="Yajun" last="Shan">Yajun Shan</name><name sortKey="Wang, Shenqi" sort="Wang, Shenqi" uniqKey="Wang S" first="Shenqi" last="Wang">Shenqi Wang</name><name sortKey="Wu, Jie" sort="Wu, Jie" uniqKey="Wu J" first="Jie" last="Wu">Jie Wu</name><name sortKey="Yao, Zhenyu" sort="Yao, Zhenyu" uniqKey="Yao Z" first="Zhenyu" last="Yao">Zhenyu Yao</name><name sortKey="Zhao, Zhenhu" sort="Zhao, Zhenhu" uniqKey="Zhao Z" first="Zhenhu" last="Zhao">Zhenhu Zhao</name></noCountry><country name="République populaire de Chine"><noRegion><name sortKey="Yuan, Xiaoling" sort="Yuan, Xiaoling" uniqKey="Yuan X" first="Xiaoling" last="Yuan">Xiaoling Yuan</name></noRegion></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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