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PXD001733

DataSet Summary

  • HostingRepository: MassIVE
  • AnnounceDate: 2015-01-26
  • AnnouncementXML: Submission_2015-01-26_18:40:46.xml
  • DigitalObjectIdentifier:
  • ReviewLevel: Non peer-reviewed dataset
  • DatasetOrigin: Original data
  • RepositorySupport: Unsupported dataset by repository
  • PrimarySubmitter: Karl Clauser
  • Title: Lenalidomide Causes Selective Degradation of IKZF1 and IKZF3 in Multiple Myeloma Cells
  • Description: Krönke J, Udeshi ND, Narla A, Grauman P, Hurst SN, McConkey M, Svinkina T, Heckl D, Comer E, Li X, Ciarlo C, Hartman E, Munshi N, Schenone M, Schreiber SL, Carr SA, Ebert BL. Science 2014, 343, 301-305. doi:10.1126/science.1244851. Lenalidomide is a drug with clinical efficacy in multiple myeloma and other B cell neoplasms, but its mechanism of action is unknown. Using quantitative proteomics, we found that lenalidomide causes selective ubiquitination and degradation of two lymphoid transcription factors, IKZF1 and IKZF3, by the CRBN-CRL4 ubiquitin ligase. IKZF1 and IKZF3 are essential transcription factors in multiple myeloma. A single amino acid substitution of IKZF3 conferred resistance to lenalidomide-induced degradation and rescued lenalidomide-induced inhibition of cell growth. Similarly, we found that lenalidomide-induced interleukin-2 production in T cells is due to depletion of IKZF1 and IKZF3. These findings reveal a previously unknown mechanism of action for a therapeutic agent: alteration of the activity of an E3 ubiquitin ligase, leading to selective degradation of specific targets.
  • SpeciesList: scientific name: Homo sapiens; common name: human; NCBI TaxID: 9606;
  • ModificationList: ubiquitination signature dipeptidyl lysine; unknown modification: C-carbamidomethyl; unknown modification: SILAC-R0K0,R6K4,R10K8; unknown modification: Protein Nterm-Acetyl; unknown modification: M-oxidation
  • Instrument: Q Exactive

Dataset History

VersionDatetimeStatusChangeLog Entry
02015-01-26 17:29:02ID requested
12015-01-26 18:40:46announced

Publication List

  1. Dataset with its publication pending

Keyword List

  1. submitter keyword: lenalidomide, ubiquitin

Contact List

    Steven A. Carr
    • lab head:
    Karl Clauser
    • contact affiliation: Broad Institute of MIT and Harvard
    • contact email: clauser@broad.mit.edu
    • dataset submitter:

Full Dataset Link List

  1. MassIVE dataset URI
  2. Dataset FTP location
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