FBXW7-Induced MTOR Degradation Forces Autophagy to Counteract Persistent Prion Infection.
Identifieur interne : 000D21 ( Main/Corpus ); précédent : 000D20; suivant : 000D22FBXW7-Induced MTOR Degradation Forces Autophagy to Counteract Persistent Prion Infection.
Auteurs : Yin Xu ; Chan Tian ; Jing Sun ; Jin Zhang ; Ke Ren ; Xue-Yu Fan ; Ke Wang ; Hui Wang ; Yu-E Yan ; Cao Chen ; Qi Shi ; Xiao-Ping DongSource :
- Molecular neurobiology [ 1559-1182 ] ; 2016.
English descriptors
- KwdEn :
- Animals (MeSH), Autophagy (physiology), Brain (metabolism), Brain (pathology), Cell Line (MeSH), Cricetinae (MeSH), F-Box Proteins (biosynthesis), F-Box-WD Repeat-Containing Protein 7 (MeSH), Mechanistic Target of Rapamycin Complex 1 (MeSH), Mesocricetus (MeSH), Mice (MeSH), Multiprotein Complexes (metabolism), PrPSc Proteins (biosynthesis), Prion Diseases (metabolism), Prion Diseases (pathology), TOR Serine-Threonine Kinases (metabolism), Ubiquitin-Protein Ligases (biosynthesis).
- MESH :
- chemical , biosynthesis : F-Box Proteins, PrPSc Proteins, Ubiquitin-Protein Ligases.
- metabolism : Brain, Multiprotein Complexes, Prion Diseases, TOR Serine-Threonine Kinases.
- pathology : Brain, Prion Diseases.
- physiology : Autophagy.
- Animals, Cell Line, Cricetinae, F-Box-WD Repeat-Containing Protein 7, Mechanistic Target of Rapamycin Complex 1, Mesocricetus, Mice.
Abstract
Autophagy is an important protein degradation pathway and a part of the innate immune system that is activated in the brain tissue during animal and human prion diseases. However, the possible mechanism by which prion infection triggers autophagy and the significance of activated autophagy on prion accumulation remain unknown. Here, we demonstrated that autophagic flux was enhanced in the persistent prion-infected cell line, SMB-S15. Knockdown of ATG5 and the presence of three autophagic inhibitors resulted in a significant increase of PrP(Sc). The mammalian target of rapamycin (MTOR) levels in SMB-S15 cells were also markedly decreased, in direct relation to PrP(Sc) accumulation. F-box and WD repeat domain containing 7 (FBXW7) levels in SMB-S15 cells and in the brains of scrapie-agent 263K-infected hamsters were upregulated at the early stage of infection, leading to active ubiquitination and degradation of MTOR. Knockdown of FBXW7 in SMB-S15 cells remarkably inhibited autophagic flux and increased PrP(Sc) accumulation. Thus, we conclude that prion infection induced the expression of FBXW7, which mediated MTOR ubiquitination and degradation, further altering phosphorylation status through cross talk between MTORC1 and AMPK and increasing autophagic flux. Autophagy may serve as innate immunity to degrade PrP(Sc) and maintain prion homeostasis.
DOI: 10.1007/s12035-014-9028-7
PubMed: 25579381
Links to Exploration step
pubmed:25579381Le document en format XML
<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">FBXW7-Induced MTOR Degradation Forces Autophagy to Counteract Persistent Prion Infection.</title><author><name sortKey="Xu, Yin" sort="Xu, Yin" uniqKey="Xu Y" first="Yin" last="Xu">Yin Xu</name><affiliation><nlm:affiliation>State Key Laboratory for Infectious Disease Prevention and Control, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases (Zhejiang University), National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Chang-Bai Rd 155, Beijing, 102206, China.</nlm:affiliation></affiliation></author><author><name sortKey="Tian, Chan" sort="Tian, Chan" uniqKey="Tian C" first="Chan" last="Tian">Chan Tian</name><affiliation><nlm:affiliation>State Key Laboratory for Infectious Disease Prevention and Control, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases (Zhejiang University), National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Chang-Bai Rd 155, Beijing, 102206, China.</nlm:affiliation></affiliation></author><author><name sortKey="Sun, Jing" sort="Sun, Jing" uniqKey="Sun J" first="Jing" last="Sun">Jing Sun</name><affiliation><nlm:affiliation>State Key Laboratory for Infectious Disease Prevention and Control, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases (Zhejiang University), National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Chang-Bai Rd 155, Beijing, 102206, China.</nlm:affiliation></affiliation></author><author><name sortKey="Zhang, Jin" sort="Zhang, Jin" uniqKey="Zhang J" first="Jin" last="Zhang">Jin Zhang</name><affiliation><nlm:affiliation>State Key Laboratory for Infectious Disease Prevention and Control, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases (Zhejiang University), National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Chang-Bai Rd 155, Beijing, 102206, China.</nlm:affiliation></affiliation></author><author><name sortKey="Ren, Ke" sort="Ren, Ke" uniqKey="Ren K" first="Ke" last="Ren">Ke Ren</name><affiliation><nlm:affiliation>State Key Laboratory for Infectious Disease Prevention and Control, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases (Zhejiang University), National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Chang-Bai Rd 155, Beijing, 102206, China.</nlm:affiliation></affiliation></author><author><name sortKey="Fan, Xue Yu" sort="Fan, Xue Yu" uniqKey="Fan X" first="Xue-Yu" last="Fan">Xue-Yu Fan</name><affiliation><nlm:affiliation>State Key Laboratory for Infectious Disease Prevention and Control, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases (Zhejiang University), National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Chang-Bai Rd 155, Beijing, 102206, China.</nlm:affiliation></affiliation></author><author><name sortKey="Wang, Ke" sort="Wang, Ke" uniqKey="Wang K" first="Ke" last="Wang">Ke Wang</name><affiliation><nlm:affiliation>State Key Laboratory for Infectious Disease Prevention and Control, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases (Zhejiang University), National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Chang-Bai Rd 155, Beijing, 102206, China.</nlm:affiliation></affiliation></author><author><name sortKey="Wang, Hui" sort="Wang, Hui" uniqKey="Wang H" first="Hui" last="Wang">Hui Wang</name><affiliation><nlm:affiliation>State Key Laboratory for Infectious Disease Prevention and Control, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases (Zhejiang University), National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Chang-Bai Rd 155, Beijing, 102206, China.</nlm:affiliation></affiliation></author><author><name sortKey="Yan, Yu E" sort="Yan, Yu E" uniqKey="Yan Y" first="Yu-E" last="Yan">Yu-E Yan</name><affiliation><nlm:affiliation>State Key Laboratory for Infectious Disease Prevention and Control, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases (Zhejiang University), National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Chang-Bai Rd 155, Beijing, 102206, China.</nlm:affiliation></affiliation></author><author><name sortKey="Chen, Cao" sort="Chen, Cao" uniqKey="Chen C" first="Cao" last="Chen">Cao Chen</name><affiliation><nlm:affiliation>State Key Laboratory for Infectious Disease Prevention and Control, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases (Zhejiang University), National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Chang-Bai Rd 155, Beijing, 102206, China.</nlm:affiliation></affiliation></author><author><name sortKey="Shi, Qi" sort="Shi, Qi" uniqKey="Shi Q" first="Qi" last="Shi">Qi Shi</name><affiliation><nlm:affiliation>State Key Laboratory for Infectious Disease Prevention and Control, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases (Zhejiang University), National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Chang-Bai Rd 155, Beijing, 102206, China.</nlm:affiliation></affiliation></author><author><name sortKey="Dong, Xiao Ping" sort="Dong, Xiao Ping" uniqKey="Dong X" first="Xiao-Ping" last="Dong">Xiao-Ping Dong</name><affiliation><nlm:affiliation>State Key Laboratory for Infectious Disease Prevention and Control, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases (Zhejiang University), National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Chang-Bai Rd 155, Beijing, 102206, China. dongxp238@sina.com.</nlm:affiliation></affiliation><affiliation><nlm:affiliation>Chinese Academy of Sciences Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing, 100101, China. dongxp238@sina.com.</nlm:affiliation></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PubMed</idno><date when="2016">2016</date><idno type="RBID">pubmed:25579381</idno><idno type="pmid">25579381</idno><idno type="doi">10.1007/s12035-014-9028-7</idno><idno type="wicri:Area/Main/Corpus">000D21</idno><idno type="wicri:explorRef" wicri:stream="Main" wicri:step="Corpus" wicri:corpus="PubMed">000D21</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en">FBXW7-Induced MTOR Degradation Forces Autophagy to Counteract Persistent Prion Infection.</title><author><name sortKey="Xu, Yin" sort="Xu, Yin" uniqKey="Xu Y" first="Yin" last="Xu">Yin Xu</name><affiliation><nlm:affiliation>State Key Laboratory for Infectious Disease Prevention and Control, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases (Zhejiang University), National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Chang-Bai Rd 155, Beijing, 102206, China.</nlm:affiliation></affiliation></author><author><name sortKey="Tian, Chan" sort="Tian, Chan" uniqKey="Tian C" first="Chan" last="Tian">Chan Tian</name><affiliation><nlm:affiliation>State Key Laboratory for Infectious Disease Prevention and Control, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases (Zhejiang University), National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Chang-Bai Rd 155, Beijing, 102206, China.</nlm:affiliation></affiliation></author><author><name sortKey="Sun, Jing" sort="Sun, Jing" uniqKey="Sun J" first="Jing" last="Sun">Jing Sun</name><affiliation><nlm:affiliation>State Key Laboratory for Infectious Disease Prevention and Control, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases (Zhejiang University), National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Chang-Bai Rd 155, Beijing, 102206, China.</nlm:affiliation></affiliation></author><author><name sortKey="Zhang, Jin" sort="Zhang, Jin" uniqKey="Zhang J" first="Jin" last="Zhang">Jin Zhang</name><affiliation><nlm:affiliation>State Key Laboratory for Infectious Disease Prevention and Control, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases (Zhejiang University), National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Chang-Bai Rd 155, Beijing, 102206, China.</nlm:affiliation></affiliation></author><author><name sortKey="Ren, Ke" sort="Ren, Ke" uniqKey="Ren K" first="Ke" last="Ren">Ke Ren</name><affiliation><nlm:affiliation>State Key Laboratory for Infectious Disease Prevention and Control, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases (Zhejiang University), National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Chang-Bai Rd 155, Beijing, 102206, China.</nlm:affiliation></affiliation></author><author><name sortKey="Fan, Xue Yu" sort="Fan, Xue Yu" uniqKey="Fan X" first="Xue-Yu" last="Fan">Xue-Yu Fan</name><affiliation><nlm:affiliation>State Key Laboratory for Infectious Disease Prevention and Control, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases (Zhejiang University), National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Chang-Bai Rd 155, Beijing, 102206, China.</nlm:affiliation></affiliation></author><author><name sortKey="Wang, Ke" sort="Wang, Ke" uniqKey="Wang K" first="Ke" last="Wang">Ke Wang</name><affiliation><nlm:affiliation>State Key Laboratory for Infectious Disease Prevention and Control, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases (Zhejiang University), National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Chang-Bai Rd 155, Beijing, 102206, China.</nlm:affiliation></affiliation></author><author><name sortKey="Wang, Hui" sort="Wang, Hui" uniqKey="Wang H" first="Hui" last="Wang">Hui Wang</name><affiliation><nlm:affiliation>State Key Laboratory for Infectious Disease Prevention and Control, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases (Zhejiang University), National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Chang-Bai Rd 155, Beijing, 102206, China.</nlm:affiliation></affiliation></author><author><name sortKey="Yan, Yu E" sort="Yan, Yu E" uniqKey="Yan Y" first="Yu-E" last="Yan">Yu-E Yan</name><affiliation><nlm:affiliation>State Key Laboratory for Infectious Disease Prevention and Control, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases (Zhejiang University), National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Chang-Bai Rd 155, Beijing, 102206, China.</nlm:affiliation></affiliation></author><author><name sortKey="Chen, Cao" sort="Chen, Cao" uniqKey="Chen C" first="Cao" last="Chen">Cao Chen</name><affiliation><nlm:affiliation>State Key Laboratory for Infectious Disease Prevention and Control, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases (Zhejiang University), National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Chang-Bai Rd 155, Beijing, 102206, China.</nlm:affiliation></affiliation></author><author><name sortKey="Shi, Qi" sort="Shi, Qi" uniqKey="Shi Q" first="Qi" last="Shi">Qi Shi</name><affiliation><nlm:affiliation>State Key Laboratory for Infectious Disease Prevention and Control, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases (Zhejiang University), National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Chang-Bai Rd 155, Beijing, 102206, China.</nlm:affiliation></affiliation></author><author><name sortKey="Dong, Xiao Ping" sort="Dong, Xiao Ping" uniqKey="Dong X" first="Xiao-Ping" last="Dong">Xiao-Ping Dong</name><affiliation><nlm:affiliation>State Key Laboratory for Infectious Disease Prevention and Control, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases (Zhejiang University), National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Chang-Bai Rd 155, Beijing, 102206, China. dongxp238@sina.com.</nlm:affiliation></affiliation><affiliation><nlm:affiliation>Chinese Academy of Sciences Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing, 100101, China. dongxp238@sina.com.</nlm:affiliation></affiliation></author></analytic><series><title level="j">Molecular neurobiology</title><idno type="eISSN">1559-1182</idno><imprint><date when="2016" type="published">2016</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Animals (MeSH)</term><term>Autophagy (physiology)</term><term>Brain (metabolism)</term><term>Brain (pathology)</term><term>Cell Line (MeSH)</term><term>Cricetinae (MeSH)</term><term>F-Box Proteins (biosynthesis)</term><term>F-Box-WD Repeat-Containing Protein 7 (MeSH)</term><term>Mechanistic Target of Rapamycin Complex 1 (MeSH)</term><term>Mesocricetus (MeSH)</term><term>Mice (MeSH)</term><term>Multiprotein Complexes (metabolism)</term><term>PrPSc Proteins (biosynthesis)</term><term>Prion Diseases (metabolism)</term><term>Prion Diseases (pathology)</term><term>TOR Serine-Threonine Kinases (metabolism)</term><term>Ubiquitin-Protein Ligases (biosynthesis)</term></keywords><keywords scheme="MESH" type="chemical" qualifier="biosynthesis" xml:lang="en"><term>F-Box Proteins</term><term>PrPSc Proteins</term><term>Ubiquitin-Protein Ligases</term></keywords><keywords scheme="MESH" qualifier="metabolism" xml:lang="en"><term>Brain</term><term>Multiprotein Complexes</term><term>Prion Diseases</term><term>TOR Serine-Threonine Kinases</term></keywords><keywords scheme="MESH" qualifier="pathology" xml:lang="en"><term>Brain</term><term>Prion Diseases</term></keywords><keywords scheme="MESH" qualifier="physiology" xml:lang="en"><term>Autophagy</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Animals</term><term>Cell Line</term><term>Cricetinae</term><term>F-Box-WD Repeat-Containing Protein 7</term><term>Mechanistic Target of Rapamycin Complex 1</term><term>Mesocricetus</term><term>Mice</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">Autophagy is an important protein degradation pathway and a part of the innate immune system that is activated in the brain tissue during animal and human prion diseases. However, the possible mechanism by which prion infection triggers autophagy and the significance of activated autophagy on prion accumulation remain unknown. Here, we demonstrated that autophagic flux was enhanced in the persistent prion-infected cell line, SMB-S15. Knockdown of ATG5 and the presence of three autophagic inhibitors resulted in a significant increase of PrP(Sc). The mammalian target of rapamycin (MTOR) levels in SMB-S15 cells were also markedly decreased, in direct relation to PrP(Sc) accumulation. F-box and WD repeat domain containing 7 (FBXW7) levels in SMB-S15 cells and in the brains of scrapie-agent 263K-infected hamsters were upregulated at the early stage of infection, leading to active ubiquitination and degradation of MTOR. Knockdown of FBXW7 in SMB-S15 cells remarkably inhibited autophagic flux and increased PrP(Sc) accumulation. Thus, we conclude that prion infection induced the expression of FBXW7, which mediated MTOR ubiquitination and degradation, further altering phosphorylation status through cross talk between MTORC1 and AMPK and increasing autophagic flux. Autophagy may serve as innate immunity to degrade PrP(Sc) and maintain prion homeostasis. </div></front></TEI><pubmed><MedlineCitation Status="MEDLINE" Owner="NLM"><PMID Version="1">25579381</PMID><DateCompleted><Year>2016</Year><Month>10</Month><Day>07</Day></DateCompleted><DateRevised><Year>2018</Year><Month>11</Month><Day>13</Day></DateRevised><Article PubModel="Print-Electronic"><Journal><ISSN IssnType="Electronic">1559-1182</ISSN><JournalIssue CitedMedium="Internet"><Volume>53</Volume><Issue>1</Issue><PubDate><Year>2016</Year><Month>Jan</Month></PubDate></JournalIssue><Title>Molecular neurobiology</Title><ISOAbbreviation>Mol Neurobiol</ISOAbbreviation></Journal><ArticleTitle>FBXW7-Induced MTOR Degradation Forces Autophagy to Counteract Persistent Prion Infection.</ArticleTitle><Pagination><MedlinePgn>706-719</MedlinePgn></Pagination><ELocationID EIdType="doi" ValidYN="Y">10.1007/s12035-014-9028-7</ELocationID><Abstract><AbstractText>Autophagy is an important protein degradation pathway and a part of the innate immune system that is activated in the brain tissue during animal and human prion diseases. However, the possible mechanism by which prion infection triggers autophagy and the significance of activated autophagy on prion accumulation remain unknown. Here, we demonstrated that autophagic flux was enhanced in the persistent prion-infected cell line, SMB-S15. Knockdown of ATG5 and the presence of three autophagic inhibitors resulted in a significant increase of PrP(Sc). The mammalian target of rapamycin (MTOR) levels in SMB-S15 cells were also markedly decreased, in direct relation to PrP(Sc) accumulation. F-box and WD repeat domain containing 7 (FBXW7) levels in SMB-S15 cells and in the brains of scrapie-agent 263K-infected hamsters were upregulated at the early stage of infection, leading to active ubiquitination and degradation of MTOR. Knockdown of FBXW7 in SMB-S15 cells remarkably inhibited autophagic flux and increased PrP(Sc) accumulation. Thus, we conclude that prion infection induced the expression of FBXW7, which mediated MTOR ubiquitination and degradation, further altering phosphorylation status through cross talk between MTORC1 and AMPK and increasing autophagic flux. Autophagy may serve as innate immunity to degrade PrP(Sc) and maintain prion homeostasis. </AbstractText></Abstract><AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Xu</LastName><ForeName>Yin</ForeName><Initials>Y</Initials><AffiliationInfo><Affiliation>State Key Laboratory for Infectious Disease Prevention and Control, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases (Zhejiang University), National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Chang-Bai Rd 155, Beijing, 102206, China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Tian</LastName><ForeName>Chan</ForeName><Initials>C</Initials><AffiliationInfo><Affiliation>State Key Laboratory for Infectious Disease Prevention and Control, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases (Zhejiang University), National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Chang-Bai Rd 155, Beijing, 102206, China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Sun</LastName><ForeName>Jing</ForeName><Initials>J</Initials><AffiliationInfo><Affiliation>State Key Laboratory for Infectious Disease Prevention and Control, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases (Zhejiang University), National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Chang-Bai Rd 155, Beijing, 102206, China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Zhang</LastName><ForeName>Jin</ForeName><Initials>J</Initials><AffiliationInfo><Affiliation>State Key Laboratory for Infectious Disease Prevention and Control, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases (Zhejiang University), National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Chang-Bai Rd 155, Beijing, 102206, China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Ren</LastName><ForeName>Ke</ForeName><Initials>K</Initials><AffiliationInfo><Affiliation>State Key Laboratory for Infectious Disease Prevention and Control, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases (Zhejiang University), National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Chang-Bai Rd 155, Beijing, 102206, China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Fan</LastName><ForeName>Xue-Yu</ForeName><Initials>XY</Initials><AffiliationInfo><Affiliation>State Key Laboratory for Infectious Disease Prevention and Control, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases (Zhejiang University), National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Chang-Bai Rd 155, Beijing, 102206, China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Wang</LastName><ForeName>Ke</ForeName><Initials>K</Initials><AffiliationInfo><Affiliation>State Key Laboratory for Infectious Disease Prevention and Control, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases (Zhejiang University), National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Chang-Bai Rd 155, Beijing, 102206, China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Wang</LastName><ForeName>Hui</ForeName><Initials>H</Initials><AffiliationInfo><Affiliation>State Key Laboratory for Infectious Disease Prevention and Control, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases (Zhejiang University), National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Chang-Bai Rd 155, Beijing, 102206, China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Yan</LastName><ForeName>Yu-E</ForeName><Initials>YE</Initials><AffiliationInfo><Affiliation>State Key Laboratory for Infectious Disease Prevention and Control, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases (Zhejiang University), National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Chang-Bai Rd 155, Beijing, 102206, China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Chen</LastName><ForeName>Cao</ForeName><Initials>C</Initials><AffiliationInfo><Affiliation>State Key Laboratory for Infectious Disease Prevention and Control, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases (Zhejiang University), National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Chang-Bai Rd 155, Beijing, 102206, China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Shi</LastName><ForeName>Qi</ForeName><Initials>Q</Initials><AffiliationInfo><Affiliation>State Key Laboratory for Infectious Disease Prevention and Control, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases (Zhejiang University), National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Chang-Bai Rd 155, Beijing, 102206, China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Dong</LastName><ForeName>Xiao-Ping</ForeName><Initials>XP</Initials><AffiliationInfo><Affiliation>State Key Laboratory for Infectious Disease Prevention and Control, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases (Zhejiang University), National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Chang-Bai Rd 155, Beijing, 102206, China. dongxp238@sina.com.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Chinese Academy of Sciences Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing, 100101, China. dongxp238@sina.com.</Affiliation></AffiliationInfo></Author></AuthorList><Language>eng</Language><PublicationTypeList><PublicationType UI="D016428">Journal Article</PublicationType><PublicationType UI="D013485">Research Support, Non-U.S. Gov't</PublicationType></PublicationTypeList><ArticleDate DateType="Electronic"><Year>2015</Year><Month>01</Month><Day>13</Day></ArticleDate></Article><MedlineJournalInfo><Country>United States</Country><MedlineTA>Mol Neurobiol</MedlineTA><NlmUniqueID>8900963</NlmUniqueID><ISSNLinking>0893-7648</ISSNLinking></MedlineJournalInfo><ChemicalList><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D044783">F-Box Proteins</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D000073979">F-Box-WD Repeat-Containing Protein 7</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="C513272">Fbxw7 protein, mouse</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D046912">Multiprotein Complexes</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D018620">PrPSc Proteins</NameOfSubstance></Chemical><Chemical><RegistryNumber>EC 2.3.2.27</RegistryNumber><NameOfSubstance UI="D044767">Ubiquitin-Protein Ligases</NameOfSubstance></Chemical><Chemical><RegistryNumber>EC 2.7.1.1</RegistryNumber><NameOfSubstance UI="D058570">TOR Serine-Threonine Kinases</NameOfSubstance></Chemical><Chemical><RegistryNumber>EC 2.7.11.1</RegistryNumber><NameOfSubstance UI="D000076222">Mechanistic Target of Rapamycin Complex 1</NameOfSubstance></Chemical></ChemicalList><CitationSubset>IM</CitationSubset><MeshHeadingList><MeshHeading><DescriptorName UI="D000818" MajorTopicYN="N">Animals</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D001343" MajorTopicYN="N">Autophagy</DescriptorName><QualifierName UI="Q000502" MajorTopicYN="Y">physiology</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D001921" MajorTopicYN="N">Brain</DescriptorName><QualifierName UI="Q000378" MajorTopicYN="N">metabolism</QualifierName><QualifierName UI="Q000473" MajorTopicYN="N">pathology</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D002460" MajorTopicYN="N">Cell Line</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D006224" MajorTopicYN="N">Cricetinae</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D044783" MajorTopicYN="N">F-Box Proteins</DescriptorName><QualifierName UI="Q000096" MajorTopicYN="Y">biosynthesis</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D000073979" MajorTopicYN="N">F-Box-WD Repeat-Containing Protein 7</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D000076222" MajorTopicYN="N">Mechanistic Target of Rapamycin Complex 1</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D008647" MajorTopicYN="N">Mesocricetus</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D051379" MajorTopicYN="N">Mice</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D046912" MajorTopicYN="N">Multiprotein Complexes</DescriptorName><QualifierName UI="Q000378" MajorTopicYN="Y">metabolism</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D018620" MajorTopicYN="N">PrPSc Proteins</DescriptorName><QualifierName UI="Q000096" MajorTopicYN="Y">biosynthesis</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D017096" MajorTopicYN="N">Prion Diseases</DescriptorName><QualifierName UI="Q000378" 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