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In historical attempts to treat morning sickness, use of 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.
Pubmed ID: 30067223 RIS Download
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A commercial antibody supplier and provider of various services.
View all literature mentionsCommercial vendor and service provider of laboratory reagents and antibodies. Supplier of scientific instrumentation, reagents and consumables, and software services.
View all literature mentionsGlobal nonprofit biological resource center (BRC) and research organization that provides biological products, technical services and educational programs to private industry, government and academic organizations. Its mission is to acquire, authenticate, preserve, develop and distribute biological materials, information, technology, intellectual property and standards for the advancement and application of scientific knowledge. The primary purpose of ATCC is to use its resources and experience as a BRC to become the world leader in standard biological reference materials management, intellectual property resource management and translational research as applied to biomaterial development, standardization and certification. ATCC characterizes cell lines, bacteria, viruses, fungi and protozoa, as well as develops and evaluates assays and techniques for validating research resources and preserving and distributing biological materials to the public and private sector research communities.
View all literature mentionsCollection of data of protein sequence and functional information. Resource for protein sequence and annotation data. Consortium for preservation of the UniProt databases: UniProt Knowledgebase (UniProtKB), UniProt Reference Clusters (UniRef), and UniProt Archive (UniParc), UniProt Proteomes. Collaboration between European Bioinformatics Institute (EMBL-EBI), SIB Swiss Institute of Bioinformatics and Protein Information Resource. Swiss-Prot is a curated subset of UniProtKB.
View all literature mentionsStatistical analysis software that combines scientific graphing, comprehensive curve fitting (nonlinear regression), understandable statistics, and data organization. Designed for biological research applications in pharmacology, physiology, and other biological fields for data analysis, hypothesis testing, and modeling.
View all literature mentionsSoftware package for the analysis of gene expression microarray data, especially the use of linear models for analyzing designed experiments and the assessment of differential expression.
View all literature mentionsA commercial antibody supplier which supplies primary and secondary antibodies, biochemicals, proteins, peptides, lysates, immunoassays and other kits.
View all literature mentionsThis monoclonal targets FLAG
View all literature mentionsThis polyclonal targets DTWD1
View all literature mentionsThis polyclonal targets Mouse Sall4
View all literature mentionsThis monoclonal targets Sall4 antibody
View all literature mentionsThis unknown targets GZF1
View all literature mentionsThis monoclonal targets GAPDH antibody produced in mouse
View all literature mentionsThis unknown targets IgG
View all literature mentionsThis polyclonal targets Streptavidin
View all literature mentionsThis polyclonal secondary targets IgG
View all literature mentionsThis unknown targets Strep•Tag® II HRP Conjugate
View all literature mentionsThis polyclonal targets IgG
View all literature mentionsCell line SK-N-DZ is a Cancer cell line with a species of origin Homo sapiens (Human)
View all literature mentionsCell line WA09 is a Embryonic stem cell with a species of origin Homo sapiens (Human)
View all literature mentionsCell line MM1.S is a Cancer cell line with a species of origin Homo sapiens (Human)
View all literature mentionsCell line BTI-Tn-5B1-4 is a Spontaneously immortalized cell line with a species of origin Trichoplusia ni (Cabbage looper)
View all literature mentionsCell line Kelly is a Cancer cell line with a species of origin Homo sapiens (Human)
View all literature mentionsCell line TC1 [Mouse ESC] is a Embryonic stem cell with a species of origin Mus musculus (Mouse)
View all literature mentionsCell line HEK293T is a Transformed cell line with a species of origin Homo sapiens (Human)
View all literature mentionsCell line NCI-H661 is a Cancer cell line with a species of origin Homo sapiens (Human)
View all literature mentionsThis polyclonal targets IgG
View all literature mentionsThis unknown targets Strep•Tag® II HRP Conjugate
View all literature mentionsThis polyclonal targets Streptavidin
View all literature mentionsThis polyclonal secondary targets IgG
View all literature mentionsThis unknown targets IgG
View all literature mentionsThis monoclonal targets GAPDH antibody produced in mouse
View all literature mentionsThis unknown targets GZF1
View all literature mentionsThis monoclonal targets FLAG
View all literature mentionsThis polyclonal targets DTWD1
View all literature mentionsThis polyclonal targets Mouse Sall4
View all literature mentionsThis monoclonal targets Sall4 antibody
View all literature mentionsCell line BTI-Tn-5B1-4 is a Spontaneously immortalized cell line with a species of origin Trichoplusia ni (Cabbage looper)
View all literature mentionsCell line TC1 [Mouse ESC] is a Embryonic stem cell with a species of origin Mus musculus (Mouse)
View all literature mentionsCell line HEK293T is a Transformed cell line with a species of origin Homo sapiens (Human)
View all literature mentionsCell line NCI-H661 is a Cancer cell line with a species of origin Homo sapiens (Human)
View all literature mentionsCell line MM1.S is a Cancer cell line with a species of origin Homo sapiens (Human)
View all literature mentionsCell line SK-N-DZ is a Cancer cell line with a species of origin Homo sapiens (Human)
View all literature mentionsCell line Kelly is a Cancer cell line with a species of origin Homo sapiens (Human)
View all literature mentionsCell line WA09 is a Embryonic stem cell with a species of origin Homo sapiens (Human)
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