Work Description

Title: WDR81 controls IKK dependent cell survival Open Access Deposited

http://creativecommons.org/licenses/by-nc/4.0/
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Abstract
  • Virus infection often results in death of the infected cells. Cell death prior to generation of virus progeny limits the spread of infection to neighboring cells and therefore can be beneficial to the host. However, cell death might also cause tissue destruction and could contribute to viral disease. It is therefore important to understand how cell death is controlled. Here, we uncover a cell death regulating role for WDR81 – a cellular protein that has not been previously implicated in affecting cell death. We find that when this protein is absent, cells express a much greater level of survival signals. These survival signals prevent efficient induction of cell death. By investigating how these survival signals are expressed, we reveal a new link between WDR81 and NFB, a well-known cellular survival pathway.
Methodology
  • A variety of virological measurements were used to measure the amount of virus (indirect immunofluorescence, RT-qPCR and plaque assays). A variety of methods were used to measure activation of cell death (microscopy and enzymatic assays). Host gene expression was measured by RNA-seq analysis.
Description
  • Apoptosis is a common host response to virus infection. The extent and timing of apoptosis following infection is controlled by the balance between the strength of signals that activate death signaling and those that promote the survival of cells. In many cell types, infection with Mammalian orthoreovirus (reovirus) results in induction of cell death by apoptosis late in infection. In this study, we uncovered that WD repeat-containing protein 81 (WDR81) is required for apoptosis induction after reovirus infection. The requirement for WDR81 for apoptosis induction is not unique to reovirus because cells lacking WDR81 are also resistant to apoptosis induced by other agonists that trigger the extrinsic apoptotic pathway. We find that in cells deficient in WDR81, expression of several pro-survival genes is upregulated. The expression of these genes is controlled by the inhibitor of kB kinase complex (IKK)-Nuclear Factor of kB (NFκB) signaling pathway. When IKK signaling is blocked in WDR81-deficient cells, pro-survival gene expression is restored to normal levels and the cells regain their susceptibility to reovirus-induced death receptor-triggered apoptosis. Our work uncovers a new function for WDR81 in controlling apoptosis. Additionally, it reveals a previously unknown link between endosomally localized protein WDR81 and IKK-NFκB signaling.
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Depositor
Contact information
Other Funding agency
  • National Institutes of Health
Citations to related material
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Resource type
Last modified
  • 03/26/2025
DOI
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To Cite this Work:
Danthi, P. WDR81 controls IKK dependent cell survival [Data set]. Indiana University - DataCORE. https://doi.org/10.5967/0yr9-0n12

Relationships

Files (Count: 19; Size: 3.44 MB)

Thumbnail Title Original Upload Last Modified File Size Access Actions
Fig_3ABC_source_data.xlsx 2025-03-25 2025-03-25 3.19 MB Open Access
Figure_1A__FFU.xlsx 2025-03-25 2025-03-25 10.6 KB Open Access
Figure_1B__titer.xlsx 2025-03-25 2025-03-25 9.17 KB Open Access
Figure_1C__cell_death.xlsx 2025-03-25 2025-03-25 10.3 KB Open Access
Figure_2A__zvad_FFU.xlsx 2025-03-25 2025-03-25 13.4 KB Open Access
Figure_2B__zvad_cell_death.xlsx 2025-03-25 2025-03-25 10.4 KB Open Access
Figure_2C__zvad_c3-7_glo.xlsx 2025-03-25 2025-03-25 12.4 KB Open Access
Figure_2D__zvad_c3-7_incucyte.xlsx 2025-03-25 2025-03-25 10.4 KB Open Access
Figure_3D__A20_qpcr.xlsx 2025-03-25 2025-03-25 19.8 KB Open Access
Figure_3E__Bcl2_qPCR.xlsx 2025-03-25 2025-03-25 27.2 KB Open Access
Figure_4A__a20_ikki_qPCR.xlsx 2025-03-25 2025-03-25 28.3 KB Open Access
Figure_4B__A20_pi3ki_qpcr.xlsx 2025-03-25 2025-03-25 28.9 KB Open Access
Figure_5A__bcl2i_cell_death.xlsx 2025-03-25 2025-03-25 10.5 KB Open Access
Figure_5B__bcl2i_c3-7_incucyte.xlsx 2025-03-25 2025-03-25 10.2 KB Open Access
Figure_5C__tnf-chx__ikki__pi3ki_....xlsx 2025-03-25 2025-03-25 10.5 KB Open Access
Figure_5D__tnf-chx__ikki__pi3ki_....xlsx 2025-03-25 2025-03-25 10.5 KB Open Access
Figure_6A__ikki_FFU.xlsx 2025-03-25 2025-03-25 12.5 KB Open Access
Figure_6B__Ikki_cell_death.xlsx 2025-03-25 2025-03-25 10.4 KB Open Access
Figure_6C__ikki_c3-7_incucyte.xlsx 2025-03-25 2025-03-25 11.6 KB Open Access

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