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PXD010420

DataSet Summary

  • HostingRepository: PRIDE
  • AnnounceDate: 2018-08-09
  • AnnouncementXML: Submission_2018-08-09_09:43:25.xml
  • DigitalObjectIdentifier:
  • ReviewLevel: Peer-reviewed dataset
  • DatasetOrigin: Original data
  • RepositorySupport: Unsupported dataset by repository
  • PrimarySubmitter: Eric Fischer
  • Title: Thalidomide promotes degradation of SALL4, a transcription factor implicated in Duane Radial Ray Syndrome, part 5
  • Description: Frequently used to treat morning sickness, the drug thalidomide led to the birth of thousands of children with severe birth defects. Despite their teratogenicity, thalidomide and related IMiD drugs are now a mainstay of cancer treatment, however, the molecular basis underlying the pleiotropic biology and characteristic birth defects remains unknown. Here we show that IMiDs disrupt a broad transcriptional network through induced degradation of several C2H2 zinc finger transcription factors, including SALL4, a member of the Spalt-like family of developmental transcription factors. Strikingly, heterozygous loss of function mutations in SALL4 result in a human developmental condition that phenocopies thalidomide induced birth defects such as absence of thumbs, phocomelia, defects in ear and eye development, and congenital heart disease. We find that thalidomide induces degradation of SALL4 exclusively in humans, primates and rabbits, but not in rodents or fish, providing a mechanistic link for the species-specific pathogenesis of thalidomide syndrome.
  • SpeciesList: scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
  • ModificationList: TMT6plex-126 reporter+balance reagent acylated residue; iodoacetamide derivatized residue
  • Instrument: Orbitrap Fusion Lumos

Dataset History

VersionDatetimeStatusChangeLog Entry
02018-07-13 02:59:53ID requested
12018-08-09 09:43:27announced

Publication List

  1. Donovan KA, An J, Nowak RP, Yuan JC, Fink EC, Berry BC, Ebert BL, Fischer ES, Thalidomide promotes degradation of SALL4, a transcription factor implicated in Duane Radial Ray syndrome. Elife, 7():(2018) [pubmed]

Keyword List

  1. submitter keyword: IMiDs, thalidomide, ubiquitin, cullin, crl4

Contact List

    Eric S. Fischer
    • contact affiliation: Department of Cancer Biology, Dana-Farber Cancer Institute, Boston, MA 02215, USA., Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA 02115, USA
    • contact email: eric_fischer@dfci.harvard.edu
    • lab head:
    Eric Fischer
    • contact affiliation: Dana-Farber Cancer Institute
    • contact email: eric_fischer@dfci.harvard.edu
    • dataset submitter:

Full Dataset Link List

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