PXD001733-1
PXD001733 is an original dataset announced via ProteomeXchange.
Dataset Summary
| 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. |
| HostingRepository | MassIVE |
| AnnounceDate | 2015-01-26 |
| AnnouncementXML | Submission_2015-01-26_18:40:46.xml |
| DigitalObjectIdentifier | |
| ReviewLevel | Non peer-reviewed dataset |
| DatasetOrigin | Original dataset |
| RepositorySupport | Unsupported dataset by repository |
| PrimarySubmitter | Karl Clauser |
| 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
| Revision | Datetime | Status | ChangeLog Entry |
|---|---|---|---|
| 0 | 2015-01-26 17:29:02 | ID requested | |
| ⏵ 1 | 2015-01-26 18:40:46 | announced |
Publication List
| Dataset with its publication pending |
Keyword List
| 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
| MassIVE dataset URI |
| Dataset FTP location NOTE: Most web browsers have now discontinued native support for FTP access within the browser window. But you can usually install another FTP app (we recommend FileZilla) and configure your browser to launch the external application when you click on this FTP link. Or otherwise, launch an app that supports FTP (like FileZilla) and use this address: ftp://MSV000079017:a@massive.ucsd.edu |
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