Suppression of Fas/APO-1-Mediated Apoptosis by Mitogen-Activated Kinase Signaling

Holmström, Tim H.; Chow, Sek C.; Elo, Iina; Coffey, Eleanor T.; Orrenius, Sten; Sistonen, Lea; Eriksson, John E.

doi:10.4049/jimmunol.160.6.2626

Cited by 100 publications

(1 citation statement)

References 62 publications

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“…Then, MMP is changed and the mitochondrial membrane becomes more permeable, allowing cytochrome c release [148][149][150]. Mitogen-activated protein kinase (MAPK)/extracellular signal-regulated kinase (ERK) can negatively regulate apoptosis by inhibiting caspase-8 and Bit activation, impeding mitochondrial depolarization, and cytochrome c release, protecting CD8+ T cells from death [149,151,152].…”

Section: Targeting Mitochondria-mediated Intrinsic Apoptosis Of Cd8+ ...mentioning

confidence: 99%

Mitochondria dysfunction in CD8+ T cells as an important contributing factor for cancer development and a potential target for cancer treatment: a review

Zhang

et al. 2022

J Exp Clin Cancer Res

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CD8+ T cells play a central role in anti-tumor immunity. Naïve CD8+ T cells are active upon tumor antigen stimulation, and then differentiate into functional cells and migrate towards the tumor sites. Activated CD8+ T cells can directly destroy tumor cells by releasing perforin and granzymes and inducing apoptosis mediated by the death ligand/death receptor. They also secrete cytokines to regulate the immune system against tumor cells. Mitochondria are the central hub of metabolism and signaling, required for polarization, and migration of CD8+ T cells. Many studies have demonstrated that mitochondrial dysfunction impairs the anti-tumor activity of CD8+ T cells through various pathways. Mitochondrial energy metabolism maladjustment will cause a cellular energy crisis in CD8+ T cells. Abnormally high levels of mitochondrial reactive oxygen species will damage the integrity and architecture of biofilms of CD8+ T cells. Disordered mitochondrial dynamics will affect the mitochondrial number and localization within cells, further affecting the function of CD8+ T cells. Increased mitochondria-mediated intrinsic apoptosis will decrease the lifespan and quantity of CD8+ T cells. Excessively low mitochondrial membrane potential will cause the release of cytochrome c and apoptosis of CD8+ T cells, while excessively high will exacerbate oxidative stress. Dysregulation of mitochondrial Ca2+ signaling will affect various physiological pathways in CD8+ T cells. To some extent, mitochondrial abnormality in CD8+ T cells contributes to cancer development. So far, targeting mitochondrial energy metabolism, mitochondrial dynamics, mitochondria-mediated cell apoptosis, and other mitochondrial physiological processes to rebuild the anti-tumor function of CD8+ T cells has proved effective in some cancer models. Thus, mitochondria in CD8+ T cells may be a potential and powerful target for cancer treatment in the future.

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Section: Targeting Mitochondria-mediated Intrinsic Apoptosis Of Cd8+ ...mentioning

confidence: 99%

Mitochondria dysfunction in CD8+ T cells as an important contributing factor for cancer development and a potential target for cancer treatment: a review

Zhang

et al. 2022

J Exp Clin Cancer Res

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Hyperphosphorylation of tau is mediated by ERK activation during anticancer drug-induced apoptosis in neuroblastoma cells

et al. 2001

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Role of CD95-activated caspase-1 processing of IL-1β in TCR-mediated proliferation of HIV-infected CD4+ T cells

Petit¹,

Corbeil²,

Lelièvre³

et al. 2001

Eur. J. Immunol.

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CD95 plays a critical role in the homeostasis of the immune system, and has been reported to participate in T cell death during HIV infection. Here we report that the response to CD3‐TCR stimulation of CD4+ T cells from HIV‐infected individuals and CD4+ T cells from healthy donors incubated in vitro with HIV‐1Lai depends on the manner the CD3‐TCR complex is engaged. While stimulation by anti‐CD3 antibodies in solution induced CD4 T cell apoptosis both in the absence or presence of anti‐CD95 antibodies, stimulation by immobilized anti‐CD3 antibodies rendered CD4+ T cells resistant to CD95‐mediated death and led to increased CD4 T cell proliferation in response to CD95 ligation. CD95 ligation of CD4+ T cells led to the activation of caspases, while costimulation induced by anti‐CD3 and anti‐CD95 mAb prevented the full processing of caspase‐3 and caspase‐8. Proliferation of CD4+ T cells induced by CD3‐TCR and CD95 costimulation was decreased by treatments with a caspase‐1 inhibitor or with neutralizing antibodies to IL‐1ß, indicating a requirement for caspase‐1‐mediated IL‐1β processing and secretion. Ourfindings suggest a novel mechanism whereby in addition to its role in inducing T cell apoptosis, CD95 signaling during HIV infection may also provide a costimulatory signal leading to an enhancement of CD4 T cell proliferation in response to CD3‐TCR complex engagement.

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Suppression of Fas/APO-1-Mediated Apoptosis by Mitogen-Activated Kinase Signaling

Cited by 100 publications

References 62 publications

Mitochondria dysfunction in CD8+ T cells as an important contributing factor for cancer development and a potential target for cancer treatment: a review

Mitochondria dysfunction in CD8+ T cells as an important contributing factor for cancer development and a potential target for cancer treatment: a review

Hyperphosphorylation of tau is mediated by ERK activation during anticancer drug-induced apoptosis in neuroblastoma cells

Role of CD95-activated caspase-1 processing of IL-1β in TCR-mediated proliferation of HIV-infected CD4+ T cells

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