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http://hdl.handle.net/10609/139238
Title: | PML-II regulates ERK and AKT signal activation and IFN alpha-induced cell death |
Author: | Meng, Xueqiong Chen, Yixiang Macip, Salvador Leppard, Keith |
Others: | Universitat Oberta de Catalunya (UOC) |
Citation: | Meng, X., Chen, Y., Macip, S. et al. PML-II regulates ERK and AKT signal activation and IFNa-induced cell death. Cell Commun Signal 19, 70 (2021). 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 IFNa-induced cell death. Methods: HeLa cells were transiently depleted of PML-II by siRNA treatment and the response of these cells to treatment with IFNa assessed by molecular assays of mRNA and proteins associated with IFN and apoptosis responses. Results: In HeLa cells, death during IFNa 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 IFNa stimulation and consequently increased resistance to IFNa-induced apoptosis. Conclusions: The positive contribution of PML-II to the expression of various IFNa-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. |
Keywords: | promyelocytic leukemia protein PML-II IFNa apoptotic signaling ERK AKT |
DOI: | https://doi.org/10.1186/s12964-021-00756-5 |
Document type: | info:eu-repo/semantics/article |
Issue Date: | 2-Jul-2021 |
Publication license: | http://creativecommons.org/licenses/by/3.0/es/ |
Appears in Collections: | Articles Articles cientÍfics |
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