The ubiquitin ligase Hrd1 promotes degradation of the Z variant alpha 1-antitrypsin and increases its solubility View Full Text


Ontology type: schema:ScholarlyArticle     


Article Info

DATE

2011-01

AUTHORS

Haiping Wang, Qi Li, Yujun Shen, Aimin Sun, Xiaoguang Zhu, Shengyun Fang, Yuxian Shen

ABSTRACT

Alpha 1-antitrypsin (AAT) deficiency is an autosomal recessive disorder that is characterized by the retention of misfolded AAT in the endoplasmic reticulum (ER) of hepatocytes and a significant decrease in the serum levels of AAT. Previous studies have demonstrated that the ubiquitin-proteasome pathway is involved in the degradation of the Z variant of AAT (ATZ). However, the detailed mechanisms of ATZ degradation are not fully understood. We investigated whether the ER membrane-embedded ubiquitin ligase (E3) Hrd1 promotes the removal of ATZ through ER-associated degradation (ERAD). Our results indicate that Hrd1 decreases intracellular levels of ATZ, especially the detergent-insoluble fraction, in cells transfected with a plasmid-encoding ATZ. The degradation of ATZ was also found to be dependent on the functional E3 activity of Hrd1. In addition, we demonstrated that Hrd1 increases the solubility of ATZ. Cycloheximide (CHX) chase and proteasome inhibition experiments showed that the ubiquitin-proteasome pathway is involved in Hrd1-mediated ATZ degradation. Furthermore, we found that Hrd1 helped to maintain normal morphology of ATZ expressing cells. These data indicate that Hrd1 enhances the removal of ATZ through ERAD and attenuates intracellular ATZ accumulation and toxicity, which implies a potential value for Hrd1 in the treatment of AAT deficiency diseases. More... »

PAGES

137-145

Identifiers

URI

http://scigraph.springernature.com/pub.10.1007/s11010-010-0600-9

DOI

http://dx.doi.org/10.1007/s11010-010-0600-9

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1018031172

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/20886262


Indexing Status Check whether this publication has been indexed by Scopus and Web Of Science using the SN Indexing Status Tool
Incoming Citations Browse incoming citations for this publication using opencitations.net

JSON-LD is the canonical representation for SciGraph data.

TIP: You can open this SciGraph record using an external JSON-LD service: JSON-LD Playground Google SDTT

[
  {
    "@context": "https://springernature.github.io/scigraph/jsonld/sgcontext.json", 
    "about": [
      {
        "id": "http://purl.org/au-research/vocabulary/anzsrc-for/2008/0601", 
        "inDefinedTermSet": "http://purl.org/au-research/vocabulary/anzsrc-for/2008/", 
        "name": "Biochemistry and Cell Biology", 
        "type": "DefinedTerm"
      }, 
      {
        "id": "http://purl.org/au-research/vocabulary/anzsrc-for/2008/06", 
        "inDefinedTermSet": "http://purl.org/au-research/vocabulary/anzsrc-for/2008/", 
        "name": "Biological Sciences", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Base Sequence", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "DNA Primers", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Humans", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Hydrolysis", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "RNA Interference", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Solubility", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Ubiquitin-Protein Ligases", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "alpha 1-Antitrypsin", 
        "type": "DefinedTerm"
      }
    ], 
    "author": [
      {
        "affiliation": {
          "alternateName": "Anhui Medical University", 
          "id": "https://www.grid.ac/institutes/grid.186775.a", 
          "name": [
            "School of Pharmacy, Anhui Medical University, 230032, Hefei, China", 
            "Key Laboratory of Gene Resource Utilization for Genetic Diseases, Ministry of Education and Anhui Province, Anhui Medical University, 230032, Hefei, China", 
            "Institute of Biopharmaceutical Research, Anhui Medical University, 230032, Hefei, China"
          ], 
          "type": "Organization"
        }, 
        "familyName": "Wang", 
        "givenName": "Haiping", 
        "id": "sg:person.0632702426.93", 
        "sameAs": [
          "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.0632702426.93"
        ], 
        "type": "Person"
      }, 
      {
        "affiliation": {
          "alternateName": "Anhui Medical University", 
          "id": "https://www.grid.ac/institutes/grid.186775.a", 
          "name": [
            "Key Laboratory of Gene Resource Utilization for Genetic Diseases, Ministry of Education and Anhui Province, Anhui Medical University, 230032, Hefei, China"
          ], 
          "type": "Organization"
        }, 
        "familyName": "Li", 
        "givenName": "Qi", 
        "type": "Person"
      }, 
      {
        "affiliation": {
          "alternateName": "Anhui Medical University", 
          "id": "https://www.grid.ac/institutes/grid.186775.a", 
          "name": [
            "Key Laboratory of Gene Resource Utilization for Genetic Diseases, Ministry of Education and Anhui Province, Anhui Medical University, 230032, Hefei, China"
          ], 
          "type": "Organization"
        }, 
        "familyName": "Shen", 
        "givenName": "Yujun", 
        "id": "sg:person.01063366364.90", 
        "sameAs": [
          "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01063366364.90"
        ], 
        "type": "Person"
      }, 
      {
        "affiliation": {
          "alternateName": "Anhui Medical University", 
          "id": "https://www.grid.ac/institutes/grid.186775.a", 
          "name": [
            "Key Laboratory of Gene Resource Utilization for Genetic Diseases, Ministry of Education and Anhui Province, Anhui Medical University, 230032, Hefei, China"
          ], 
          "type": "Organization"
        }, 
        "familyName": "Sun", 
        "givenName": "Aimin", 
        "id": "sg:person.0704753447.42", 
        "sameAs": [
          "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.0704753447.42"
        ], 
        "type": "Person"
      }, 
      {
        "affiliation": {
          "alternateName": "Bengbu Medical College", 
          "id": "https://www.grid.ac/institutes/grid.252957.e", 
          "name": [
            "Department of Pharmacology, Bengbu Medical College, 233030, Bengbu, China"
          ], 
          "type": "Organization"
        }, 
        "familyName": "Zhu", 
        "givenName": "Xiaoguang", 
        "id": "sg:person.0753066647.34", 
        "sameAs": [
          "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.0753066647.34"
        ], 
        "type": "Person"
      }, 
      {
        "affiliation": {
          "alternateName": "University of Maryland, College Park", 
          "id": "https://www.grid.ac/institutes/grid.164295.d", 
          "name": [
            "Medical Biotechnology Center, University of Maryland Biotechnology Institute, 21201, Baltimore, MD, USA"
          ], 
          "type": "Organization"
        }, 
        "familyName": "Fang", 
        "givenName": "Shengyun", 
        "id": "sg:person.01055511500.23", 
        "sameAs": [
          "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01055511500.23"
        ], 
        "type": "Person"
      }, 
      {
        "affiliation": {
          "alternateName": "Anhui Medical University", 
          "id": "https://www.grid.ac/institutes/grid.186775.a", 
          "name": [
            "School of Pharmacy, Anhui Medical University, 230032, Hefei, China", 
            "Key Laboratory of Gene Resource Utilization for Genetic Diseases, Ministry of Education and Anhui Province, Anhui Medical University, 230032, Hefei, China", 
            "Institute of Biopharmaceutical Research, Anhui Medical University, 230032, Hefei, China"
          ], 
          "type": "Organization"
        }, 
        "familyName": "Shen", 
        "givenName": "Yuxian", 
        "id": "sg:person.0625034500.19", 
        "sameAs": [
          "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.0625034500.19"
        ], 
        "type": "Person"
      }
    ], 
    "citation": [
      {
        "id": "https://doi.org/10.1016/s0959-440x(96)80060-1", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1001750735"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1016/j.jmb.2007.10.055", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1002242428"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1056/nejmcp0900449", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1003203933"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1074/jbc.m103703200", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1004092306"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1074/jbc.272.1.510", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1008073630"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1073/pnas.1430537100", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1009477870"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.1038/ncb1689", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1009760622", 
          "https://doi.org/10.1038/ncb1689"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1073/pnas.0506618103", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1013072838"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1074/jbc.272.1.217", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1013170362"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1074/jbc.m313701200", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1016185188"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1074/jbc.m105226200", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1017367525"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1038/sj.emboj.7601974", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1018949084"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1002/hep.21822", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1022401147"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1073/pnas.251401598", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1022626134"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1136/thx.2003.006502", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1024470756"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1136/thx.2003.006502", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1024470756"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1083/jcb.200312018", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1025704988"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1074/jbc.270.15.8393", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1026069890"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1111/j.1742-4658.2007.05639.x", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1026332198"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1016/s0014-5793(02)03660-8", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1027239365"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1016/j.bbrc.2006.08.173", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1028079180"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1074/jbc.m509409200", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1030264928"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1378/chest.122.5.1818", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1031958513"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1378/chest.122.5.1818", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1031958513"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1091/mbc.7.12.2029", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1038940690"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.1038/nbt0991-825", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1043020989", 
          "https://doi.org/10.1038/nbt0991-825"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1074/jbc.m508652200", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1045429983"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1074/jbc.m508652200", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1045429983"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1074/jbc.m607976200", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1046045803"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1152/ajpgi.00237.2004", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1047065987"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.1038/nmeth979", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1048092216", 
          "https://doi.org/10.1038/nmeth979"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.1038/nmeth979", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1048092216", 
          "https://doi.org/10.1038/nmeth979"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1038/sj.emboj.7601490", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1048351137"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.1038/357605a0", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1048738506", 
          "https://doi.org/10.1038/357605a0"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1016/j.yexcr.2006.10.031", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1051066361"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1074/jbc.270.15.8597", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1051448031"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1254/jphs.08005fp", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1052511755"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1126/science.165.3894.709", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1062497681"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1172/jci16782", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1063415535"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.4161/auto.2882", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1072290042"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1152/ajpgi.2000.278.1.g39", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1074579981"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1152/ajpgi.2000.279.5.g961", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1074719153"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://app.dimensions.ai/details/publication/pub.1079646175", 
        "type": "CreativeWork"
      }
    ], 
    "datePublished": "2011-01", 
    "datePublishedReg": "2011-01-01", 
    "description": "Alpha 1-antitrypsin (AAT) deficiency is an autosomal recessive disorder that is characterized by the retention of misfolded AAT in the endoplasmic reticulum (ER) of hepatocytes and a significant decrease in the serum levels of AAT. Previous studies have demonstrated that the ubiquitin-proteasome pathway is involved in the degradation of the Z variant of AAT (ATZ). However, the detailed mechanisms of ATZ degradation are not fully understood. We investigated whether the ER membrane-embedded ubiquitin ligase (E3) Hrd1 promotes the removal of ATZ through ER-associated degradation (ERAD). Our results indicate that Hrd1 decreases intracellular levels of ATZ, especially the detergent-insoluble fraction, in cells transfected with a plasmid-encoding ATZ. The degradation of ATZ was also found to be dependent on the functional E3 activity of Hrd1. In addition, we demonstrated that Hrd1 increases the solubility of ATZ. Cycloheximide (CHX) chase and proteasome inhibition experiments showed that the ubiquitin-proteasome pathway is involved in Hrd1-mediated ATZ degradation. Furthermore, we found that Hrd1 helped to maintain normal morphology of ATZ expressing cells. These data indicate that Hrd1 enhances the removal of ATZ through ERAD and attenuates intracellular ATZ accumulation and toxicity, which implies a potential value for Hrd1 in the treatment of AAT deficiency diseases.", 
    "genre": "research_article", 
    "id": "sg:pub.10.1007/s11010-010-0600-9", 
    "inLanguage": [
      "en"
    ], 
    "isAccessibleForFree": false, 
    "isFundedItemOf": [
      {
        "id": "sg:grant.4941453", 
        "type": "MonetaryGrant"
      }, 
      {
        "id": "sg:grant.4946435", 
        "type": "MonetaryGrant"
      }
    ], 
    "isPartOf": [
      {
        "id": "sg:journal.1016672", 
        "issn": [
          "0300-8177", 
          "1573-4919"
        ], 
        "name": "Molecular and Cellular Biochemistry", 
        "type": "Periodical"
      }, 
      {
        "issueNumber": "1-2", 
        "type": "PublicationIssue"
      }, 
      {
        "type": "PublicationVolume", 
        "volumeNumber": "346"
      }
    ], 
    "name": "The ubiquitin ligase Hrd1 promotes degradation of the Z variant alpha 1-antitrypsin and increases its solubility", 
    "pagination": "137-145", 
    "productId": [
      {
        "name": "readcube_id", 
        "type": "PropertyValue", 
        "value": [
          "55e9c0c3b133bd8210d34786c9d17ba6b2c4f8e0dab6e118372e04f55c3d21f7"
        ]
      }, 
      {
        "name": "pubmed_id", 
        "type": "PropertyValue", 
        "value": [
          "20886262"
        ]
      }, 
      {
        "name": "nlm_unique_id", 
        "type": "PropertyValue", 
        "value": [
          "0364456"
        ]
      }, 
      {
        "name": "doi", 
        "type": "PropertyValue", 
        "value": [
          "10.1007/s11010-010-0600-9"
        ]
      }, 
      {
        "name": "dimensions_id", 
        "type": "PropertyValue", 
        "value": [
          "pub.1018031172"
        ]
      }
    ], 
    "sameAs": [
      "https://doi.org/10.1007/s11010-010-0600-9", 
      "https://app.dimensions.ai/details/publication/pub.1018031172"
    ], 
    "sdDataset": "articles", 
    "sdDatePublished": "2019-04-11T10:54", 
    "sdLicense": "https://scigraph.springernature.com/explorer/license/", 
    "sdPublisher": {
      "name": "Springer Nature - SN SciGraph project", 
      "type": "Organization"
    }, 
    "sdSource": "s3://com-uberresearch-data-dimensions-target-20181106-alternative/cleanup/v134/2549eaecd7973599484d7c17b260dba0a4ecb94b/merge/v9/a6c9fde33151104705d4d7ff012ea9563521a3ce/jats-lookup/v90/0000000351_0000000351/records_43252_00000000.jsonl", 
    "type": "ScholarlyArticle", 
    "url": "http://link.springer.com/10.1007%2Fs11010-010-0600-9"
  }
]
 

Download the RDF metadata as:  json-ld nt turtle xml License info

HOW TO GET THIS DATA PROGRAMMATICALLY:

JSON-LD is a popular format for linked data which is fully compatible with JSON.

curl -H 'Accept: application/ld+json' 'https://scigraph.springernature.com/pub.10.1007/s11010-010-0600-9'

N-Triples is a line-based linked data format ideal for batch operations.

curl -H 'Accept: application/n-triples' 'https://scigraph.springernature.com/pub.10.1007/s11010-010-0600-9'

Turtle is a human-readable linked data format.

curl -H 'Accept: text/turtle' 'https://scigraph.springernature.com/pub.10.1007/s11010-010-0600-9'

RDF/XML is a standard XML format for linked data.

curl -H 'Accept: application/rdf+xml' 'https://scigraph.springernature.com/pub.10.1007/s11010-010-0600-9'


 

This table displays all metadata directly associated to this object as RDF triples.

274 TRIPLES      21 PREDICATES      76 URIs      29 LITERALS      17 BLANK NODES

Subject Predicate Object
1 sg:pub.10.1007/s11010-010-0600-9 schema:about N1c681dd1cb9e443cb2885fc13880f76b
2 N4dfe9133b3a740f5aa75693bb68d0c8a
3 N6fce6b64be244c868200965c74562f5c
4 N8ee23fadc2cf4669a224b70a83b36d80
5 Na79ae56705ef470fb0e93d3c057b1b01
6 Nbe5896975de849d3816b7735cb43b518
7 Nc807491349c644d78e01b0e0652fd6da
8 Nc85aad20e9254177a603b4b5b4889474
9 anzsrc-for:06
10 anzsrc-for:0601
11 schema:author Ndc93da8a9ff24f54bbf7e8596f347654
12 schema:citation sg:pub.10.1038/357605a0
13 sg:pub.10.1038/nbt0991-825
14 sg:pub.10.1038/ncb1689
15 sg:pub.10.1038/nmeth979
16 https://app.dimensions.ai/details/publication/pub.1079646175
17 https://doi.org/10.1002/hep.21822
18 https://doi.org/10.1016/j.bbrc.2006.08.173
19 https://doi.org/10.1016/j.jmb.2007.10.055
20 https://doi.org/10.1016/j.yexcr.2006.10.031
21 https://doi.org/10.1016/s0014-5793(02)03660-8
22 https://doi.org/10.1016/s0959-440x(96)80060-1
23 https://doi.org/10.1038/sj.emboj.7601490
24 https://doi.org/10.1038/sj.emboj.7601974
25 https://doi.org/10.1056/nejmcp0900449
26 https://doi.org/10.1073/pnas.0506618103
27 https://doi.org/10.1073/pnas.1430537100
28 https://doi.org/10.1073/pnas.251401598
29 https://doi.org/10.1074/jbc.270.15.8393
30 https://doi.org/10.1074/jbc.270.15.8597
31 https://doi.org/10.1074/jbc.272.1.217
32 https://doi.org/10.1074/jbc.272.1.510
33 https://doi.org/10.1074/jbc.m103703200
34 https://doi.org/10.1074/jbc.m105226200
35 https://doi.org/10.1074/jbc.m313701200
36 https://doi.org/10.1074/jbc.m508652200
37 https://doi.org/10.1074/jbc.m509409200
38 https://doi.org/10.1074/jbc.m607976200
39 https://doi.org/10.1083/jcb.200312018
40 https://doi.org/10.1091/mbc.7.12.2029
41 https://doi.org/10.1111/j.1742-4658.2007.05639.x
42 https://doi.org/10.1126/science.165.3894.709
43 https://doi.org/10.1136/thx.2003.006502
44 https://doi.org/10.1152/ajpgi.00237.2004
45 https://doi.org/10.1152/ajpgi.2000.278.1.g39
46 https://doi.org/10.1152/ajpgi.2000.279.5.g961
47 https://doi.org/10.1172/jci16782
48 https://doi.org/10.1254/jphs.08005fp
49 https://doi.org/10.1378/chest.122.5.1818
50 https://doi.org/10.4161/auto.2882
51 schema:datePublished 2011-01
52 schema:datePublishedReg 2011-01-01
53 schema:description Alpha 1-antitrypsin (AAT) deficiency is an autosomal recessive disorder that is characterized by the retention of misfolded AAT in the endoplasmic reticulum (ER) of hepatocytes and a significant decrease in the serum levels of AAT. Previous studies have demonstrated that the ubiquitin-proteasome pathway is involved in the degradation of the Z variant of AAT (ATZ). However, the detailed mechanisms of ATZ degradation are not fully understood. We investigated whether the ER membrane-embedded ubiquitin ligase (E3) Hrd1 promotes the removal of ATZ through ER-associated degradation (ERAD). Our results indicate that Hrd1 decreases intracellular levels of ATZ, especially the detergent-insoluble fraction, in cells transfected with a plasmid-encoding ATZ. The degradation of ATZ was also found to be dependent on the functional E3 activity of Hrd1. In addition, we demonstrated that Hrd1 increases the solubility of ATZ. Cycloheximide (CHX) chase and proteasome inhibition experiments showed that the ubiquitin-proteasome pathway is involved in Hrd1-mediated ATZ degradation. Furthermore, we found that Hrd1 helped to maintain normal morphology of ATZ expressing cells. These data indicate that Hrd1 enhances the removal of ATZ through ERAD and attenuates intracellular ATZ accumulation and toxicity, which implies a potential value for Hrd1 in the treatment of AAT deficiency diseases.
54 schema:genre research_article
55 schema:inLanguage en
56 schema:isAccessibleForFree false
57 schema:isPartOf N5d5cfa3d90394ff7aaad80e937e2f72d
58 N79982200de864b848c2716d1ec8b7375
59 sg:journal.1016672
60 schema:name The ubiquitin ligase Hrd1 promotes degradation of the Z variant alpha 1-antitrypsin and increases its solubility
61 schema:pagination 137-145
62 schema:productId Na4736085213c40dc999ad61765479597
63 Nbd1dc878a88b493a8a0744dda8842ae9
64 Ne0cd76e2edcc4c4693f5bf6c609c04aa
65 Ne7dd10d05f0b47f49fedbc41dd4867b6
66 Ned09325e304b402eb825e0b93487dc2c
67 schema:sameAs https://app.dimensions.ai/details/publication/pub.1018031172
68 https://doi.org/10.1007/s11010-010-0600-9
69 schema:sdDatePublished 2019-04-11T10:54
70 schema:sdLicense https://scigraph.springernature.com/explorer/license/
71 schema:sdPublisher N57ff62c74ed14a38acb80ced70215a07
72 schema:url http://link.springer.com/10.1007%2Fs11010-010-0600-9
73 sgo:license sg:explorer/license/
74 sgo:sdDataset articles
75 rdf:type schema:ScholarlyArticle
76 N007f27ca99674c6da18ede4f0baeb0fa schema:affiliation https://www.grid.ac/institutes/grid.186775.a
77 schema:familyName Li
78 schema:givenName Qi
79 rdf:type schema:Person
80 N1c681dd1cb9e443cb2885fc13880f76b schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
81 schema:name RNA Interference
82 rdf:type schema:DefinedTerm
83 N3ad2512c0afd4b189b734af50be5659a rdf:first sg:person.0753066647.34
84 rdf:rest N734f156db48f48759f19fde4e448d2aa
85 N4dfe9133b3a740f5aa75693bb68d0c8a schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
86 schema:name Hydrolysis
87 rdf:type schema:DefinedTerm
88 N5238832ad29f43769d22771352ec3db8 rdf:first sg:person.0625034500.19
89 rdf:rest rdf:nil
90 N57ff62c74ed14a38acb80ced70215a07 schema:name Springer Nature - SN SciGraph project
91 rdf:type schema:Organization
92 N5d5cfa3d90394ff7aaad80e937e2f72d schema:volumeNumber 346
93 rdf:type schema:PublicationVolume
94 N6fce6b64be244c868200965c74562f5c schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
95 schema:name Base Sequence
96 rdf:type schema:DefinedTerm
97 N734f156db48f48759f19fde4e448d2aa rdf:first sg:person.01055511500.23
98 rdf:rest N5238832ad29f43769d22771352ec3db8
99 N79982200de864b848c2716d1ec8b7375 schema:issueNumber 1-2
100 rdf:type schema:PublicationIssue
101 N8ee23fadc2cf4669a224b70a83b36d80 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
102 schema:name alpha 1-Antitrypsin
103 rdf:type schema:DefinedTerm
104 N9aef603511c449b8b486fa5936214812 rdf:first sg:person.01063366364.90
105 rdf:rest Nba3bb9dbf2f440a3be42dc14dadfb302
106 Na4736085213c40dc999ad61765479597 schema:name readcube_id
107 schema:value 55e9c0c3b133bd8210d34786c9d17ba6b2c4f8e0dab6e118372e04f55c3d21f7
108 rdf:type schema:PropertyValue
109 Na79ae56705ef470fb0e93d3c057b1b01 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
110 schema:name Solubility
111 rdf:type schema:DefinedTerm
112 Nba3bb9dbf2f440a3be42dc14dadfb302 rdf:first sg:person.0704753447.42
113 rdf:rest N3ad2512c0afd4b189b734af50be5659a
114 Nbd1dc878a88b493a8a0744dda8842ae9 schema:name pubmed_id
115 schema:value 20886262
116 rdf:type schema:PropertyValue
117 Nbe5896975de849d3816b7735cb43b518 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
118 schema:name Ubiquitin-Protein Ligases
119 rdf:type schema:DefinedTerm
120 Nc807491349c644d78e01b0e0652fd6da schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
121 schema:name Humans
122 rdf:type schema:DefinedTerm
123 Nc85aad20e9254177a603b4b5b4889474 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
124 schema:name DNA Primers
125 rdf:type schema:DefinedTerm
126 Ndc93da8a9ff24f54bbf7e8596f347654 rdf:first sg:person.0632702426.93
127 rdf:rest Nfe2e525b62d64a7f832a99be279f0ab2
128 Ne0cd76e2edcc4c4693f5bf6c609c04aa schema:name nlm_unique_id
129 schema:value 0364456
130 rdf:type schema:PropertyValue
131 Ne7dd10d05f0b47f49fedbc41dd4867b6 schema:name dimensions_id
132 schema:value pub.1018031172
133 rdf:type schema:PropertyValue
134 Ned09325e304b402eb825e0b93487dc2c schema:name doi
135 schema:value 10.1007/s11010-010-0600-9
136 rdf:type schema:PropertyValue
137 Nfe2e525b62d64a7f832a99be279f0ab2 rdf:first N007f27ca99674c6da18ede4f0baeb0fa
138 rdf:rest N9aef603511c449b8b486fa5936214812
139 anzsrc-for:06 schema:inDefinedTermSet anzsrc-for:
140 schema:name Biological Sciences
141 rdf:type schema:DefinedTerm
142 anzsrc-for:0601 schema:inDefinedTermSet anzsrc-for:
143 schema:name Biochemistry and Cell Biology
144 rdf:type schema:DefinedTerm
145 sg:grant.4941453 http://pending.schema.org/fundedItem sg:pub.10.1007/s11010-010-0600-9
146 rdf:type schema:MonetaryGrant
147 sg:grant.4946435 http://pending.schema.org/fundedItem sg:pub.10.1007/s11010-010-0600-9
148 rdf:type schema:MonetaryGrant
149 sg:journal.1016672 schema:issn 0300-8177
150 1573-4919
151 schema:name Molecular and Cellular Biochemistry
152 rdf:type schema:Periodical
153 sg:person.01055511500.23 schema:affiliation https://www.grid.ac/institutes/grid.164295.d
154 schema:familyName Fang
155 schema:givenName Shengyun
156 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01055511500.23
157 rdf:type schema:Person
158 sg:person.01063366364.90 schema:affiliation https://www.grid.ac/institutes/grid.186775.a
159 schema:familyName Shen
160 schema:givenName Yujun
161 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01063366364.90
162 rdf:type schema:Person
163 sg:person.0625034500.19 schema:affiliation https://www.grid.ac/institutes/grid.186775.a
164 schema:familyName Shen
165 schema:givenName Yuxian
166 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.0625034500.19
167 rdf:type schema:Person
168 sg:person.0632702426.93 schema:affiliation https://www.grid.ac/institutes/grid.186775.a
169 schema:familyName Wang
170 schema:givenName Haiping
171 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.0632702426.93
172 rdf:type schema:Person
173 sg:person.0704753447.42 schema:affiliation https://www.grid.ac/institutes/grid.186775.a
174 schema:familyName Sun
175 schema:givenName Aimin
176 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.0704753447.42
177 rdf:type schema:Person
178 sg:person.0753066647.34 schema:affiliation https://www.grid.ac/institutes/grid.252957.e
179 schema:familyName Zhu
180 schema:givenName Xiaoguang
181 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.0753066647.34
182 rdf:type schema:Person
183 sg:pub.10.1038/357605a0 schema:sameAs https://app.dimensions.ai/details/publication/pub.1048738506
184 https://doi.org/10.1038/357605a0
185 rdf:type schema:CreativeWork
186 sg:pub.10.1038/nbt0991-825 schema:sameAs https://app.dimensions.ai/details/publication/pub.1043020989
187 https://doi.org/10.1038/nbt0991-825
188 rdf:type schema:CreativeWork
189 sg:pub.10.1038/ncb1689 schema:sameAs https://app.dimensions.ai/details/publication/pub.1009760622
190 https://doi.org/10.1038/ncb1689
191 rdf:type schema:CreativeWork
192 sg:pub.10.1038/nmeth979 schema:sameAs https://app.dimensions.ai/details/publication/pub.1048092216
193 https://doi.org/10.1038/nmeth979
194 rdf:type schema:CreativeWork
195 https://app.dimensions.ai/details/publication/pub.1079646175 schema:CreativeWork
196 https://doi.org/10.1002/hep.21822 schema:sameAs https://app.dimensions.ai/details/publication/pub.1022401147
197 rdf:type schema:CreativeWork
198 https://doi.org/10.1016/j.bbrc.2006.08.173 schema:sameAs https://app.dimensions.ai/details/publication/pub.1028079180
199 rdf:type schema:CreativeWork
200 https://doi.org/10.1016/j.jmb.2007.10.055 schema:sameAs https://app.dimensions.ai/details/publication/pub.1002242428
201 rdf:type schema:CreativeWork
202 https://doi.org/10.1016/j.yexcr.2006.10.031 schema:sameAs https://app.dimensions.ai/details/publication/pub.1051066361
203 rdf:type schema:CreativeWork
204 https://doi.org/10.1016/s0014-5793(02)03660-8 schema:sameAs https://app.dimensions.ai/details/publication/pub.1027239365
205 rdf:type schema:CreativeWork
206 https://doi.org/10.1016/s0959-440x(96)80060-1 schema:sameAs https://app.dimensions.ai/details/publication/pub.1001750735
207 rdf:type schema:CreativeWork
208 https://doi.org/10.1038/sj.emboj.7601490 schema:sameAs https://app.dimensions.ai/details/publication/pub.1048351137
209 rdf:type schema:CreativeWork
210 https://doi.org/10.1038/sj.emboj.7601974 schema:sameAs https://app.dimensions.ai/details/publication/pub.1018949084
211 rdf:type schema:CreativeWork
212 https://doi.org/10.1056/nejmcp0900449 schema:sameAs https://app.dimensions.ai/details/publication/pub.1003203933
213 rdf:type schema:CreativeWork
214 https://doi.org/10.1073/pnas.0506618103 schema:sameAs https://app.dimensions.ai/details/publication/pub.1013072838
215 rdf:type schema:CreativeWork
216 https://doi.org/10.1073/pnas.1430537100 schema:sameAs https://app.dimensions.ai/details/publication/pub.1009477870
217 rdf:type schema:CreativeWork
218 https://doi.org/10.1073/pnas.251401598 schema:sameAs https://app.dimensions.ai/details/publication/pub.1022626134
219 rdf:type schema:CreativeWork
220 https://doi.org/10.1074/jbc.270.15.8393 schema:sameAs https://app.dimensions.ai/details/publication/pub.1026069890
221 rdf:type schema:CreativeWork
222 https://doi.org/10.1074/jbc.270.15.8597 schema:sameAs https://app.dimensions.ai/details/publication/pub.1051448031
223 rdf:type schema:CreativeWork
224 https://doi.org/10.1074/jbc.272.1.217 schema:sameAs https://app.dimensions.ai/details/publication/pub.1013170362
225 rdf:type schema:CreativeWork
226 https://doi.org/10.1074/jbc.272.1.510 schema:sameAs https://app.dimensions.ai/details/publication/pub.1008073630
227 rdf:type schema:CreativeWork
228 https://doi.org/10.1074/jbc.m103703200 schema:sameAs https://app.dimensions.ai/details/publication/pub.1004092306
229 rdf:type schema:CreativeWork
230 https://doi.org/10.1074/jbc.m105226200 schema:sameAs https://app.dimensions.ai/details/publication/pub.1017367525
231 rdf:type schema:CreativeWork
232 https://doi.org/10.1074/jbc.m313701200 schema:sameAs https://app.dimensions.ai/details/publication/pub.1016185188
233 rdf:type schema:CreativeWork
234 https://doi.org/10.1074/jbc.m508652200 schema:sameAs https://app.dimensions.ai/details/publication/pub.1045429983
235 rdf:type schema:CreativeWork
236 https://doi.org/10.1074/jbc.m509409200 schema:sameAs https://app.dimensions.ai/details/publication/pub.1030264928
237 rdf:type schema:CreativeWork
238 https://doi.org/10.1074/jbc.m607976200 schema:sameAs https://app.dimensions.ai/details/publication/pub.1046045803
239 rdf:type schema:CreativeWork
240 https://doi.org/10.1083/jcb.200312018 schema:sameAs https://app.dimensions.ai/details/publication/pub.1025704988
241 rdf:type schema:CreativeWork
242 https://doi.org/10.1091/mbc.7.12.2029 schema:sameAs https://app.dimensions.ai/details/publication/pub.1038940690
243 rdf:type schema:CreativeWork
244 https://doi.org/10.1111/j.1742-4658.2007.05639.x schema:sameAs https://app.dimensions.ai/details/publication/pub.1026332198
245 rdf:type schema:CreativeWork
246 https://doi.org/10.1126/science.165.3894.709 schema:sameAs https://app.dimensions.ai/details/publication/pub.1062497681
247 rdf:type schema:CreativeWork
248 https://doi.org/10.1136/thx.2003.006502 schema:sameAs https://app.dimensions.ai/details/publication/pub.1024470756
249 rdf:type schema:CreativeWork
250 https://doi.org/10.1152/ajpgi.00237.2004 schema:sameAs https://app.dimensions.ai/details/publication/pub.1047065987
251 rdf:type schema:CreativeWork
252 https://doi.org/10.1152/ajpgi.2000.278.1.g39 schema:sameAs https://app.dimensions.ai/details/publication/pub.1074579981
253 rdf:type schema:CreativeWork
254 https://doi.org/10.1152/ajpgi.2000.279.5.g961 schema:sameAs https://app.dimensions.ai/details/publication/pub.1074719153
255 rdf:type schema:CreativeWork
256 https://doi.org/10.1172/jci16782 schema:sameAs https://app.dimensions.ai/details/publication/pub.1063415535
257 rdf:type schema:CreativeWork
258 https://doi.org/10.1254/jphs.08005fp schema:sameAs https://app.dimensions.ai/details/publication/pub.1052511755
259 rdf:type schema:CreativeWork
260 https://doi.org/10.1378/chest.122.5.1818 schema:sameAs https://app.dimensions.ai/details/publication/pub.1031958513
261 rdf:type schema:CreativeWork
262 https://doi.org/10.4161/auto.2882 schema:sameAs https://app.dimensions.ai/details/publication/pub.1072290042
263 rdf:type schema:CreativeWork
264 https://www.grid.ac/institutes/grid.164295.d schema:alternateName University of Maryland, College Park
265 schema:name Medical Biotechnology Center, University of Maryland Biotechnology Institute, 21201, Baltimore, MD, USA
266 rdf:type schema:Organization
267 https://www.grid.ac/institutes/grid.186775.a schema:alternateName Anhui Medical University
268 schema:name Institute of Biopharmaceutical Research, Anhui Medical University, 230032, Hefei, China
269 Key Laboratory of Gene Resource Utilization for Genetic Diseases, Ministry of Education and Anhui Province, Anhui Medical University, 230032, Hefei, China
270 School of Pharmacy, Anhui Medical University, 230032, Hefei, China
271 rdf:type schema:Organization
272 https://www.grid.ac/institutes/grid.252957.e schema:alternateName Bengbu Medical College
273 schema:name Department of Pharmacology, Bengbu Medical College, 233030, Bengbu, China
274 rdf:type schema:Organization
 




Preview window. Press ESC to close (or click here)


...