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| Status |
Public on Sep 01, 2016 |
| Title |
Targeting Non-proteolytic Protein Ubiquitination for the Treatment of Diffuse Large B Cell Lymphoma (Agilent Arrays) |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by array
|
| Summary |
Chronic active B cell receptor (BCR) signaling, a hallmark of the ABC subtype of diffuse large B cell lymphoma (DLBCL), engages the CARD11-MALT1-BCL10 (CBM) adapter complex to activates IkappaB kinase (IKK) and the classical NF-kappaB pathway. Here we show that the CBM complex includes the E3 ubiquitin ligases cIAP1 and cIAP2, which are essential mediators of BCR-dependent NF-kappaB activity in ABC DLBCL. cIAP1/2 attach K63-linked polyubiquitin chains on themselves and on BCL10, resulting in the recruitment of IKK and the linear ubiquitin chain ligase LUBAC, which is essential for IKK activation. SMAC mimetic drugs target cIAP1/2 for destruction, and consequently suppress NF-kappaB and selectively kill BCR-dependent ABC DLBCL lines, supporting their clinical evaluation in patients with ABC DLBCL.
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| |
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| Overall design |
Samples from four ABC DLBCL cell lines (HBL1, TMD8, OCILY3, and OCILY10) were exposed to 2.5 uM birinapant for 2, 4, 6, and 24 hours (n=16). Samples from 2 ABC DLBCL cell lines (HBL1 and TMD8) were transduced with shRNA and induced with doxycycline for 3 and 4 days (n=4).
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| |
|
| Citation(s) |
27070702 |
| Submission date |
Sep 21, 2015 |
| Last update date |
May 17, 2019 |
| Contact name |
Louis M. Staudt |
| E-mail(s) |
lstaudt@mail.nih.gov
|
| Phone |
301-402-1892
|
| Organization name |
National Cancer Institute
|
| Department |
Lymphoid Malignancies Branch
|
| Lab |
Louis M Staudt
|
| Street address |
9000 Rockville Pike, Bldg 10, Rm 4N114
|
| City |
Bethesda |
| State/province |
MD |
| ZIP/Postal code |
20892 |
| Country |
USA |
| |
|
| Platforms (2) |
| GPL13607 |
Agilent-028004 SurePrint G3 Human GE 8x60K Microarray (Feature Number version) |
| GPL16699 |
Agilent-039494 SurePrint G3 Human GE v2 8x60K Microarray 039381 (Feature Number version) |
|
| Samples (20)
|
| GSM1890017 |
HBL1 Birinapant Treated - 2 hours - mAdbID:128793 |
| GSM1890018 |
HBL1 Birinapant Treated - 4 hours - mAdbID:128794 |
| GSM1890019 |
HBL1 Birinapant Treated - 6 hours - mAdbID:128795 |
| GSM1890020 |
HBL1 Birinapant Treated - 24 hours - mAdbID:128796 |
| GSM1890021 |
TMD8 Birinapant Treated - 2 hours - mAdbID:128797 |
| GSM1890022 |
TMD8 Birinapant Treated - 4 hours - mAdbID:128798 |
| GSM1890023 |
TMD8 Birinapant Treated - 6 hours - mAdbID:128799 |
| GSM1890024 |
TMD8 Birinapant Treated - 24 hours - mAdbID:128800 |
| GSM1890025 |
OCILY3 Birinapant Treated - 2 hours - mAdbID:128859 |
| GSM1890026 |
OCILY3 Birinapant Treated - 4 hours - mAdbID:128860 |
| GSM1890027 |
OCILY3 Birinapant Treated - 6 hours - mAdbID:128861 |
| GSM1890028 |
OCILY3 Birinapant Treated - 24 hours - mAdbID:128862 |
| GSM1890029 |
OCILY10 Birinapant Treated - 2 hours - mAdbID:128863 |
| GSM1890030 |
OCILY10 Birinapant Treated - 4 hours - mAdbID:128864 |
| GSM1890031 |
OCILY10 Birinapant Treated - 6 hours - mAdbID:128865 |
| GSM1890032 |
OCILY10 Birinapant Treated - 24 hours - mAdbID:128866 |
| GSM2037048 |
TMD8 shcIAP1/2 - 3 days - mAdbID:129698 |
| GSM2037049 |
TMD8 shcIAP1/2 - 4 days - mAdbID:129699 |
| GSM2037050 |
HBL1 shcIAP1/2 - 3 days - mAdbID:129700 |
| GSM2037051 |
HBL1 shcIAP1/2 - 4 days - mAdbID:129701 |
|
| Relations |
| BioProject |
PRJNA296518 |
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