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PML-II regulates ERK and AKT signal activation and IFNα-induced cell death
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Meng, Xueqiong, Chen, Yixiang, Macip, Salvador and Leppard, Keith (2021) PML-II regulates ERK and AKT signal activation and IFNα-induced cell death. Cell Communication and Signaling, 19 . 70. doi:10.1186/s12964-021-00756-5 ISSN 1478-811X.
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WRAP-PML-II-regulates-ERK-AKT-signal-IFN-induced-cell-death-2021.pdf - Published Version - Requires a PDF viewer. Available under License Creative Commons Attribution 4.0. Download (2254Kb) | Preview |
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WRAP-PML-II-regulates-ERK-AKT-signal-IFNα-induced-cell-death-2021.pdf - Accepted Version Embargoed item. Restricted access to Repository staff only - Requires a PDF viewer. Download (2458Kb) |
Official URL: https://doi.org/10.1186/s12964-021-00756-5
Abstract
Background
The requirement of promyelocytic leukaemia protein (PML) in interferon (IFN)-induced cell apoptosis is well-established. However, the exact mechanisms by which the multiple isoforms of PML protein participate in this process remain not well-understood. We previously demonstrated that PML isoform II (PML-II) positively regulates induced gene expression during a type I IFN response and evaluate here how PML-II contributes to IFNα-induced cell death.
Methods
HeLa cells were transiently depleted of PML-II by siRNA treatment and the response of these cells to treatment with IFNα assessed by molecular assays of mRNA and proteins associated with IFN and apoptosis responses.
Results
In HeLa cells, death during IFNα stimulation was reduced by prior PML-II depletion. PML-II removal also considerably decreased the induced expression of pro-apoptotic ISGs such as ISG54 (IFIT2), and substantially impaired or prevented expression of PUMA and TRAIL, proteins that are associated with the intrinsic and extrinsic apoptotic pathways respectively. Thirdly, PML-II depletion enhanced ERK and AKT pro-survival signaling activation suggesting that PML-II normally suppresses signaling via these pathways, and that lack of PML-II hence led to greater than normal activation of AKT signaling upon IFNα stimulation and consequently increased resistance to IFNα-induced apoptosis.
Conclusions
The positive contribution of PML-II to the expression of various IFNα-induced pro-apoptotic proteins and its inhibition of pro-survival signaling together provide a mechanistic explanation for reduced apoptosis under conditions of PML deficiency and may account for at least part of the role of PML as a tumor suppressor gene.
Item Type: | Journal Article | |||||||||||||||
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Subjects: | Q Science > QH Natural history > QH301 Biology Q Science > QR Microbiology > QR180 Immunology R Medicine > RC Internal medicine > RC0254 Neoplasms. Tumors. Oncology (including Cancer) |
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Divisions: | Faculty of Science, Engineering and Medicine > Science > Life Sciences (2010- ) | |||||||||||||||
Library of Congress Subject Headings (LCSH): | Tumor suppressor proteins, Apoptosis, Immune response -- Molecular aspects | |||||||||||||||
Journal or Publication Title: | Cell Communication and Signaling | |||||||||||||||
Publisher: | BMC | |||||||||||||||
ISSN: | 1478-811X | |||||||||||||||
Official Date: | 2 July 2021 | |||||||||||||||
Dates: |
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Volume: | 19 | |||||||||||||||
Article Number: | 70 | |||||||||||||||
DOI: | 10.1186/s12964-021-00756-5 | |||||||||||||||
Status: | Peer Reviewed | |||||||||||||||
Publication Status: | Published | |||||||||||||||
Access rights to Published version: | Open Access (Creative Commons) | |||||||||||||||
Date of first compliant deposit: | 22 June 2021 | |||||||||||||||
Date of first compliant Open Access: | 6 July 2021 | |||||||||||||||
RIOXX Funder/Project Grant: |
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