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PXD010417

PXD010417 is an original dataset announced via ProteomeXchange.

Dataset Summary
TitleThalidomide promotes degradation of SALL4, a transcription factor implicated in Duane Radial Ray Syndrome, part 2
DescriptionFrequently 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.
HostingRepositoryPRIDE
AnnounceDate2018-08-09
AnnouncementXMLSubmission_2018-08-09_09:55:03.xml
DigitalObjectIdentifier
ReviewLevelPeer-reviewed dataset
DatasetOriginOriginal dataset
RepositorySupportUnsupported dataset by repository
PrimarySubmitterEric Fischer
SpeciesList scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationListTMT6plex-126 reporter+balance reagent acylated residue; iodoacetamide derivatized residue
InstrumentOrbitrap Fusion Lumos
Dataset History
RevisionDatetimeStatusChangeLog Entry
02018-07-13 02:59:23ID requested
12018-08-09 09:55:04announced
Publication List
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
curator keyword: Biomedical
submitter keyword: IMiDs, thalidomide, ubiquitin, cullin, crl4
Contact List
Eric S. Fischer
contact affiliationDepartment 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 emaileric_fischer@dfci.harvard.edu
lab head
Eric Fischer
contact affiliationDana-Farber Cancer Institute
contact emaileric_fischer@dfci.harvard.edu
dataset submitter
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Dataset FTP location
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