E-GEOD-46973 - IkB-like protein NFKBIZ regulates NF-kB signaling and is critical for survival of ABC DLBCL (MALT inhibition)

Released on 22 July 2013, last updated on 13 May 2014
Homo sapiens
Samples (8)
Array (1)
Protocols (7)
Constitutive activation of the nuclear factor-kappa B (NF-kB) pathway is a hallmark of the activated B-cell-like (ABC) subtype of diffuse large B-cell lymphoma (DLBCL). Recurrent mutations of NF-kB regulators that cause constitutive activity of this oncogenic pathway have been identified. However, it remains unclear how specific target genes are regulated. We identified the IkB-like protein NFKBIZ that binds NF-kB subunits and enhances transactivation of some NF-kB target genes while repressing others, to be upregulated in ACB compared to GCB DLBCL primary patient samples (p=5.1 x 10^-37). Knockdown of NFKBIZ by RNA interference was toxic to ABC but not GCB DLBCL cell lines. Gene expression profiling following NFKBIZ knockdown significantly downregulated a large number of NF-kB target genes, suggesting a central role in regulating NF-kB signaling. To further investigate the molecular mechanisms of how NFKBIZ mediates NF-kB signaling in ABC DLBCL, we performed immunoprecipitations and detected an interaction of NFKBIZ with both p50 and p52 NF-kB subunits, indicating that both the canonical and non-canonical NF-kB pathways are regulated by NFKBIZ. Collectively, our data imply that NFKBIZ is required for NF-kB signaling in ABC DLBCL and thus might represent a promising molecular target for future therapies. The complete dataset is comprised of three experiments with the male HBL-1 ABC DLBCL cell line: a) 8 paired GEP measurements after NFKBIZ inhibition by shRNA, b) 6 paired GEP measurements after applying the MLN inhibitor and c) 4 two-color measurements after applying a MALT inhibitor. This dataset includes 4 two-color measurements of the male HBL-1 ABC DLBCL cell line after applying a MALT inhibitor.
Experiment type
transcription profiling by array 
Investigation descriptionE-GEOD-46973.idf.txt
Sample and data relationshipE-GEOD-46973.sdrf.txt
Raw data (1)E-GEOD-46973.raw.1.zip
Processed data (1)E-GEOD-46973.processed.1.zip
Array designA-AGIL-28.adf.txt