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Review
. 2021 Nov 2;7(1):104.
doi: 10.1038/s41421-021-00323-9.

Interplay between ADP-ribosyltransferases and essential cell signaling pathways controls cellular responses

Flurina Boehi #  1   2 , Patrick Manetsch #  1   3 , Michael O Hottiger  4
Affiliations
Review

Interplay between ADP-ribosyltransferases and essential cell signaling pathways controls cellular responses

Flurina Boehi et al. Cell Discov. .

Abstract

Signaling cascades provide integrative and interactive frameworks that allow the cell to respond to signals from its environment and/or from within the cell itself. The dynamic regulation of mammalian cell signaling pathways is often modulated by cascades of protein post-translational modifications (PTMs). ADP-ribosylation is a PTM that is catalyzed by ADP-ribosyltransferases and manifests as mono- (MARylation) or poly- (PARylation) ADP-ribosylation depending on the addition of one or multiple ADP-ribose units to protein substrates. ADP-ribosylation has recently emerged as an important cell regulator that impacts a plethora of cellular processes, including many intracellular signaling events. Here, we provide an overview of the interplay between the intracellular diphtheria toxin-like ADP-ribosyltransferase (ARTD) family members and five selected signaling pathways (including NF-κB, JAK/STAT, Wnt-β-catenin, MAPK, PI3K/AKT), which are frequently described to control or to be controlled by ADP-ribosyltransferases and how these interactions impact the cellular responses.

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Conflict of interest statement

The authors declare no competing interests.

Figures

Fig. 1
Fig. 1. Schematic overview of the interplay between NF-κB signaling and ARTD family members.
Canonical (left panel) and non-canoncial (right panel) pathway. Positive regulations of NF-κB signaling by ARTD family members are depicted in green, while negative effects of ARTDs on the signaling pathway are shown in red. Solid lines indicate the contribution of ADP-ribosylation to the regulation of NF-κB signaling. In case the contribution of ADP-ribosylation was not described or the protein itself rather than its enzymatic activity is involved in the regulation, the interactions are represented by dashed lines.
Fig. 2
Fig. 2. Schematic overview of the interplay between JAK/STAT signaling and ARTD family members.
Positive regulations of JAK/STAT signaling by ARTD family members are depicted in green, while negative effects of ARTDs on the signaling pathway are shown in red. Solid lines indicate the contribution of ADP-ribosylation to the regulation of JAK/STAT signaling. In case the contribution of ADP-ribosylation was not described or the protein itself rather than its enzymatic activity is involved in the regulation, the interactions are represented by dashed lines.
Fig. 3
Fig. 3. Schematic overview of the interplay between Wnt/β-catenin signaling and ARTD family members.
Uninduced (left panel) and induced (right panel) Wnt/β-catenin signaling. Positive regulations of Wnt/β-catenin signaling by ARTD family members are depicted in green. Solid lines indicate the contribution of ADP-ribosylation to the regulation of Wnt/β-catenin signaling. In case the contribution of ADP-ribosylation was not described or the protein itself rather than its enzymatic activity is involved in the regulation, the interactions are represented by dashed lines. (TNKS1/2, Tankyrase1/2).
Fig. 4
Fig. 4. Schematic overview of the interplay between MAPK signaling and ARTD family members.
Positive regulations of MAPK signaling by ARTD family members are depicted in green, while negative effects of ARTDs on the signaling pathway are shown in red. Solid lines indicate the contribution of ADP-ribosylation to the regulation of MAPK signaling (TNKS1/2, Tankyrase1/2; Ser, Serine; Thr, Threonine).
Fig. 5
Fig. 5. Schematic overview of the interplay between AKT signaling and ARTD family members.
Positive regulations of AKT signaling by ARTD family members are depicted in green, while negative effects of ARTDs on the signaling pathway are shown in red. Solid lines indicate the contribution of ADP-ribosylation or competition for substrate in the regulation of AKT signaling. In case the contribution of ADP-ribosylation was not described or the protein itself rather than its enzymatic activity is involved in the regulation, the interactions are represented by dashed lines.
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