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| Status |
Public on May 13, 2014 |
| Title |
CRL4(CRBN) ubiquitin ligase profiling |
| Organism |
Homo sapiens |
| Experiment type |
Protein profiling by protein array
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| Summary |
In the 1950s the drug thalidomide administered as a sedative to pregnant women led ot the birth of thousands of children with multiple defects. Despite its teratogenicity, thalidomide and ist IMiD derivatives recently emerged as effective treatments for multiple myeloma and 5q-dysplasia. IMiDs target the CUL4-RBX1-DDB1-CRBN (CRL4(CRBN)) ubiquitin ligase.
Through an unbiased screen we identify the homeobox trranscription factor MEIS2 as an endogenous substrate of CRL4(CRBN).
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| Overall design |
By definition, a specific target of CRL4(CRBN) is expected to have a very low intensity on negative control arrays (E1_E2), (E1_CRBN), (E1_E2_Cdt2), (E1_E2_Cdt2_revlimid), (E1_E2_Cdt2_CSN) or with CRL4(CRBN) in presence of inhibitor (E1_E2_CRBN_revlimid) and high intensity on arrays with CRL4(CRBN) (E1_E2_CRBN) or CRL4(CRBN) in presence of CSN (E1_E2_CRBN_CSN)
Accordingly 16 protein microarrays were subjected to in vitro ubiquitylation using the following enzyme combinations:
3x Uba1+UbcH5a; 2x Uba1+UbcH5a+CRL4(DDB2); 3x Uba1+UbcH5a+CRL4(CRBN); 2x Uba1+UbcH5a+CRL4(CRBN)+lenalidomide; 2x Uba1+UbcH5a+CRL4(CRBN)+CSN; 2x Uba1+UbcH5a+CRL4(Cdt2); 1x Uba1+UbcH5a+CRL4(Cdt2)+CSN; 1x Uba1+UbcH5a+CRL4(Cdt2)+lenalidomide
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| Contributor(s) |
Fischer ES, Stadler MB, Thoma NH |
| Citation(s) |
25043012 |
| Submission date |
May 12, 2014 |
| Last update date |
Jul 31, 2014 |
| Contact name |
Eric S Fischer |
| E-mail(s) |
eric_fischer@dfci.harvard.edu
|
| Phone |
+16175829281
|
| Organization name |
Dana-Farber Cancer Institute
|
| Department |
Cancer Biology
|
| Lab |
Fischer
|
| Street address |
450 Brookline Ave
|
| City |
Boston |
| State/province |
Massachusetts |
| ZIP/Postal code |
02215 |
| Country |
USA |
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| Platforms (1) |
| GPL14689 |
Invitrogen ProtoArray v5.0 (full array layout) |
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| Samples (16)
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| Relations |
| BioProject |
PRJNA246700 |
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