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

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.

PARP7-mediated ADP-ribosylation of FRA1 promotes cancer cell growth by repressing IRF1- and IRF3-dependent apoptosis

“…ADP-ribosyltransferases (ARTs) are important regulators of the cellular immune response ( 1 – 3 ). The diphtheria toxin-like ARTs (also known as ARTD subfamily) comprise an enzyme family of 17 members and catalyze the transfer of ADP-ribose moieties from nicotinamide adenine dinucleotide (NAD + ) to amino acids on target proteins (mono-ADP-ribosylation).…”

Therapeutic Approaches Targeting Cancer Stem Cells

“…The Janus kinase/signal transducer and activator of transcription (JAK/STAT) signalling pathway contributes to a variety of biological processes such as embryonic development, stem cell maintenance, haematopoiesis and inflammatory response [126]. It is known that the JAK family in mammals comprises four members (JAK1, JAK2, JAK3 and tyrosine kinase 2 (TYK2)) and that the STAT family in mammals consists of seven members (STAT1, STAT2, STAT3, STAT4, STAT5a, STAT5b and STAT6) [127]. The JAK/STAT signalling pathway is initiated by the binding of cytokines to their corresponding receptors [128].…”

Graft-Versus-Host Disease: Pathogenesis and Treatment

“…The Janus kinase/signal transducer and activator of transcription (JAK/STAT) signaling pathways are regarded as a central communication junction for the immune system [74]. In the JAK/STAT signaling pathways, the cytoplasmatic kinase JAKs interact with the transcription factor STATs, and more than 50 cytokines and growth factors are involved in the JAK/STAT signaling pathways [75]. Mammals have 4 JAKs (JAK1, JAK2, JAK3, JAK4) and 7 STATs (STAT1, STAT2, STAT3, STAT4, STAT5a, STAT5b, STAT6) [76], and the dysregulated JAK/STAT signaling pathways contribute to a variety of human diseases, which makes this signaling a promising drug target [77].…”