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Modulation of CD95-mediated signaling by post-translational modifications: towards understanding CD95 signaling networks

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Abstract

CD95 is a member of the death receptor family and is well-known to promote apoptosis. However, accumulating evidence indicates that in some context CD95 has not only the potential to induce apoptosis but also can trigger non-apoptotic signal leading to cell survival, proliferation, cancer growth and metastasis. Despite extensive investigations focused on alterations in the expression level of CD95 and associated signal molecules, very few studies, however, have investigated the effects of post-translational modifications such as glycosylation, phosphorylation, palmitoylation, nitrosylation and glutathionylation on CD95 function. Post-translational modifications of CD95 in mammalian systems are likely to play a more prominent role than anticipated in CD95 induced cell death. In this review we will focus on the alterations in CD95-mediated signaling caused by post-translational modifications of CD95.

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Abbreviations

DR:

Death receptor

TNF-R:

Tumor necrosis factor receptor

CD95:

Cluster of differentiation 95

FADD:

Fas-associated protein with death domain

c-FLIP:

Cellular FLICE inhibitory protein

DISC:

Death-inducing signaling complex

DD:

Death domain

DED:

Death effector domain

MOMP:

Mitochondrial outer membrane permeabilisation

Bid:

BH3 interacting-domain death agonist

tBid:

Truncated Bid

ERK:

Extracellular signal-regulated kinase

NF-κB:

Nuclear factor κB

CD95L:

CD95 ligand

CRD:

Cysteine-rich domain

NK:

Natural killer

EGFR:

Epidermal growth factor receptor

EGF:

Epidermal growth factor

pEGFR:

Phosphorylated EGFR

pSTAT3:

Phosphorylated STAT3

SHP-1:

Src homology domain 2 (SH2)-containing tyrosine phosphatase-1

NO:

Nitric oxide

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Acknowledgements

We acknowledge Volkswagen Foundation (VW 90315), Wilhelm Sander-Stiftung (2017.008.01), Center of dynamic systems (CDS), funded by the EU-programme ERDF (European Regional Development Fund) and DFG (LA 2386) for supporting our work.

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  1. Translational Inflammation Research, Institute of Experimental Internal Medicine, Medical Faculty, Otto von Guericke University, Magdeburg, Germany

    Kamil Seyrek & Inna N. Lavrik

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  1. Kamil Seyrek
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Correspondence to Inna N. Lavrik.

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Seyrek, K., Lavrik, I.N. Modulation of CD95-mediated signaling by post-translational modifications: towards understanding CD95 signaling networks. Apoptosis 24, 385–394 (2019). https://doi.org/10.1007/s10495-019-01540-0

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