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| Status |
Public on Jul 22, 2013 |
| Title |
IkB-like protein NFKBIZ regulates NF-kB signaling and is critical for survival of ABC DLBCL (MLN inhibition) |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by array
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| Summary |
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.
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| Overall design |
This dataset includes 6 paired GEP measurements after applying the MLN inhibitor.
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| Contributor(s) |
Lenz G |
| Citation(s) |
23869088 |
| Submission date |
May 15, 2013 |
| Last update date |
Aug 13, 2018 |
| Contact name |
Michael Grau |
| Organization name |
University of Münster
|
| Department |
Faculty of Medicine
|
| Lab |
Translational Oncology
|
| Street address |
Albert-Schweitzer-Campus 1
|
| City |
Münster |
| State/province |
Nordrhein-Westfalen |
| ZIP/Postal code |
48149 |
| Country |
Germany |
| |
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| Platforms (1) |
| GPL10558 |
Illumina HumanHT-12 V4.0 expression beadchip |
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| Samples (12)
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| This SubSeries is part of SuperSeries: |
| GSE46974 |
IkB-like protein NFKBIZ regulates NF-kB signaling and is critical for survival of ABC DLBCL |
|
| Relations |
| BioProject |
PRJNA203203 |
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