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| Status |
Public on Jun 12, 2017 |
| Title |
An autoregulatory RelB:p50 NF-κB pathway perpetuates pro-survival TNF response in multiple myeloma |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by array
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| Summary |
Pro-inflammatory cytokines were shown to promote growth and survival of cancerous cells. TNF induced RelA:p50 NF-κB dimer via the canonical pathway is thought to link inflammation with cancer. Integrating biochemical and computational studies we identify that deficiency of non-canonical signal transducer p100 triggers a positive autoregulatory loop, which instead perpetuates an alternate RelB:p50 containing NF-κB activity upon TNF treatment. TNF stimulated RelB:p50 dimer is sufficient for mediating NF-κB target gene-expressions and suppressing apoptotic cellular death independent of principal NF-κB subunit RelA. We further demonstrate that activating mutations in non-canonical NF-κB module deplete multiple myeloma cells of p100, thereby, provoking autoregulatory RelB:p50 activation. Finally, autoregulatory control reinforces protracted pro-survival NF-κB response, albeit comprising of RelB:p50, upon TNF priming that protects myeloma cells with dysfunctional p100 from subsequent apoptotic insults. In sum, we present evidence for positive autoregulation mediated through the NF-κB system and its potential involvement in human neoplasm.
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| Overall design |
Total RNA isolated from biological replicate samples comprising of untreated and 6h TNF (10ng/ml) treated WT, Rela-/-Nfkb2-/- and Rela-/-Relb-/-Rel-/- MEFs were analyzed for global gene expression levels
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| Contributor(s) |
Basak S, Roy P, Chatterjee B, Sarkar UA |
| Citation(s) |
27641334 |
| |
| Submission date |
May 06, 2015 |
| Last update date |
Jun 14, 2018 |
| Contact name |
Soumen Basak |
| Organization name |
National Institute of Immunology
|
| Department |
Infection and immunity
|
| Lab |
Systems Immunology Laboratory
|
| Street address |
Aruna Asaf Ali Marg
|
| City |
New Delhi |
| State/province |
Delhi |
| ZIP/Postal code |
110067 |
| Country |
India |
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| Platforms (1) |
| GPL6885 |
Illumina MouseRef-8 v2.0 expression beadchip |
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| Samples (12)
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| Relations |
| BioProject |
PRJNA283207 |
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