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Series GSE73281 Query DataSets for GSE73281
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.
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).
Citation(s) 27070702
Submission date Sep 21, 2015
Last update date May 17, 2019
Contact name Louis M. Staudt
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
BioProject PRJNA296518

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Supplementary file Size Download File type/resource
GSE73281_RAW.tar 426.2 Mb (http)(custom) TAR (of TXT)
Processed data included within Sample table

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