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ORF10-Cullin-2-ZYG11B complex is not required for SARS-CoV-2 infection.
Mena, Elijah L; Donahue, Callie J; Vaites, Laura Pontano; Li, Jie; Rona, Gergely; O'Leary, Colin; Lignitto, Luca; Miwatani-Minter, Bearach; Paulo, Joao A; Dhabaria, Avantika; Ueberheide, Beatrix; Gygi, Steven P; Pagano, Michele; Harper, J Wade; Davey, Robert A; Elledge, Stephen J.
  • Mena EL; Division of Genetics, Department of Genetics, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115.
  • Donahue CJ; Howard Hughes Medical Institute, Brigham and Women's Hospital, Boston, MA 02115.
  • Vaites LP; Department of Microbiology, National Emerging Infectious Disease Laboratories, Boston University Medical Campus, Boston, MA 02118.
  • Li J; Department of Cell Biology, Blavatnik Institute, Harvard Medical School, Boston, MA 02115.
  • Rona G; Department of Biochemistry and Molecular Pharmacology, New York University Grossman School of Medicine, New York, NY 10016.
  • O'Leary C; Department of Biochemistry and Molecular Pharmacology, New York University Grossman School of Medicine, New York, NY 10016.
  • Lignitto L; Howard Hughes Medical Institute, New York University Grossman School of Medicine, New York, NY 10016.
  • Miwatani-Minter B; Division of Genetics, Department of Genetics, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115.
  • Paulo JA; Department of Biochemistry and Molecular Pharmacology, New York University Grossman School of Medicine, New York, NY 10016.
  • Dhabaria A; Department of Biochemistry and Molecular Pharmacology, New York University Grossman School of Medicine, New York, NY 10016.
  • Ueberheide B; Department of Cell Biology, Blavatnik Institute, Harvard Medical School, Boston, MA 02115.
  • Gygi SP; Department of Biochemistry and Molecular Pharmacology, New York University Grossman School of Medicine, New York, NY 10016.
  • Pagano M; Proteomics Laboratory, Division of Advanced Research Technologies, New York University Grossman School of Medicine, New York, NY 10016.
  • Harper JW; Department of Biochemistry and Molecular Pharmacology, New York University Grossman School of Medicine, New York, NY 10016.
  • Davey RA; Proteomics Laboratory, Division of Advanced Research Technologies, New York University Grossman School of Medicine, New York, NY 10016.
  • Elledge SJ; Department of Neurology, New York University Grossman School of Medicine, New York, NY 10016.
Proc Natl Acad Sci U S A ; 118(17)2021 04 27.
Article in English | MEDLINE | ID: covidwho-1172591
Semantic information from SemMedBD (by NLM)
1. Proteins COEXISTS_WITH Viral Genome
Subject
Proteins
Predicate
COEXISTS_WITH
Object
Viral Genome
2. 2019 novel coronavirus NEG_COEXISTS_WITH Genus: Coronavirus
Subject
2019 novel coronavirus
Predicate
NEG_COEXISTS_WITH
Object
Genus: Coronavirus
3. ZYG11B gene|ZYG11B AFFECTS Protein Degradatio
Subject
ZYG11B gene|ZYG11B
Predicate
AFFECTS
Object
Protein Degradatio
4. Cultured Cell Line LOCATION_OF ZYG11B gene|ZYG11B
Subject
Cultured Cell Line
Predicate
LOCATION_OF
Object
ZYG11B gene|ZYG11B
5. ZER1 gene|ZER1 INTERACTS_WITH ZYG11B gene|ZYG11B
Subject
ZER1 gene|ZER1
Predicate
INTERACTS_WITH
Object
ZYG11B gene|ZYG11B
6. Proteins COEXISTS_WITH Viral Genome
Subject
Proteins
Predicate
COEXISTS_WITH
Object
Viral Genome
7. 2019 novel coronavirus NEG_COEXISTS_WITH Genus: Coronavirus
Subject
2019 novel coronavirus
Predicate
NEG_COEXISTS_WITH
Object
Genus: Coronavirus
8. ZYG11B gene|ZYG11B AFFECTS Protein Degradation, Metabolic
Subject
ZYG11B gene|ZYG11B
Predicate
AFFECTS
Object
Protein Degradation, Metabolic
9. Cultured Cell Line LOCATION_OF ZYG11B gene|ZYG11B
Subject
Cultured Cell Line
Predicate
LOCATION_OF
Object
ZYG11B gene|ZYG11B
10. ZER1 gene|ZER1 INTERACTS_WITH ZYG11B gene|ZYG11B
Subject
ZER1 gene|ZER1
Predicate
INTERACTS_WITH
Object
ZYG11B gene|ZYG11B
ABSTRACT
In order to understand the transmission and virulence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), it is necessary to understand the functions of each of the gene products encoded in the viral genome. One feature of the SARS-CoV-2 genome that is not present in related, common coronaviruses is ORF10, a putative 38-amino acid protein-coding gene. Proteomic studies found that ORF10 binds to an E3 ubiquitin ligase containing Cullin-2, Rbx1, Elongin B, Elongin C, and ZYG11B (CRL2ZYG11B). Since CRL2ZYG11B mediates protein degradation, one possible role for ORF10 is to "hijack" CRL2ZYG11B in order to target cellular, antiviral proteins for ubiquitylation and subsequent proteasomal degradation. Here, we investigated whether ORF10 hijacks CRL2ZYG11B or functions in other ways, for example, as an inhibitor or substrate of CRL2ZYG11B While we confirm the ORF10-ZYG11B interaction and show that the N terminus of ORF10 is critical for it, we find no evidence that ORF10 is functioning to inhibit or hijack CRL2ZYG11B Furthermore, ZYG11B and its paralog ZER1 are dispensable for SARS-CoV-2 infection in cultured cells. We conclude that the interaction between ORF10 and CRL2ZYG11B is not relevant for SARS-CoV-2 infection in vitro.
Subject(s)
Keywords

Full text: Available Collection: International databases Database: MEDLINE Main subject: Viral Proteins / Open Reading Frames / Cell Cycle Proteins / Cullin Proteins / Multiprotein Complexes / SARS-CoV-2 / COVID-19 Limits: Humans Language: English Year: 2021 Document Type: Article

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Full text: Available Collection: International databases Database: MEDLINE Main subject: Viral Proteins / Open Reading Frames / Cell Cycle Proteins / Cullin Proteins / Multiprotein Complexes / SARS-CoV-2 / COVID-19 Limits: Humans Language: English Year: 2021 Document Type: Article