Regulation of Wnt/β‐catenin signalling by tankyrase‐dependent poly(ADP‐ribosyl)ation and scaffolding

Mariotti, Laura; Pollock, Katie; Guettler, Sebastian

doi:10.1111/bph.14038

Cited by 112 publications

(122 citation statements)

References 165 publications

(360 reference statements)

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“…Another group of emerging drugs targeting the WNT pathway that went through several rounds of refinement is tankyrase inhibitors, small molecules that prevent the poly‐ADP‐ribosylation of axin, thereby blocking WNT/β‐catenin signalling. Sebastian Guettler and co‐workers describe cell biological mechanisms of tankyrase‐mediated ADP ribosylation of axin, structure–function relationships of tankyrase and inhibitors and put the current knowledge for potential use, for example, for the treatment of colon cancer (Mariotti et al ., ).…”

Section: Wnt2016@brno – the 2016 International Wnt Meeting At Masarykmentioning

confidence: 97%

WNT signalling: mechanisms and therapeutic opportunities

Schulte

Bryja

2017

British J Pharmacology

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At the same time as the mechanistic understanding of the WNT signalling system, with its family of 19 secreted lipoglycoproteins, 10 class Frizzled GPCRs (FZD 1-10 ), several single transmembrane-spanning receptors [LDL receptorrelated protein 5/6 (LRP5/6), ROR1/2, RYK and PTK7] and a plethora of extracellular modulators [Dickkopfs (DKKs), SFRPs, WIFs, etc.] at the core of the pathway, is improving it becomes obvious that targeting this system therapeutically comes both with great potential and substantial challenges. This themed section about WNT signalling in the British Journal of Pharmacology aims to underline the progress in our more and more detailed understanding of signalling mechanisms, to summarize emerging concepts for therapy and to highlight novel developments with therapeutic potential. In addition, we aim to bridge the scientific disciplines of cell biology, developmental biology, stem cell biology, oncology, drug development and pharmacology in order to promote a truly translational approach with the goal of obtaining more effective drugs, with higher selectivity and less unwanted side effects, for treating various human diseases. WNT2016@Brno -The 2016International WNT Meeting at Masaryk University, Brno, CZThe WNT meeting in Brno, the city of Gregor Johann Mendel, the founder of genetics, was a continuation of the EMBO conference series on WNT signalling and provided a broad overview of the exciting developments in the research field ranging from deeper structural and molecular insights to disease mechanisms and novel drug targets. In addition, this meeting marks the end of a successful international training network (WntsApp -www.wntsapp.eu) funded by the frame programme FP7 and the Marie Curie Actions/European Commission, in which several members of the conference's organizing committee and participants collaborated. Given the substantial and exciting progress in areas such as establishment and use of organoid cultures, receptor dynamics, WNT secretion, stem cell regulation, single-cell sequencing, novel treatment paradigms for human disease and drug development, an atmosphere of optimism and ambition was present at the meeting. The

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Section: Wnt2016@brno – the 2016 International Wnt Meeting At Masarykmentioning

confidence: 97%

WNT signalling: mechanisms and therapeutic opportunities

Schulte

Bryja

2017

British J Pharmacology

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“…Iduna ubiquitinates and degrades AIF, thereby preventing cell death [107]. Iduna also binds Axin immediately after Axin PARylation by tankyrase, and ubiquitinates it, leading to activation of Wnt signaling [108,109]. Iduna acts on PARP1-and tankyrase-dependent PARylated proteins; whereas PARP1 modifies proteins with long and complex PAR chains, tankyrase adds short and low complexity of PAR to proteins.…”

Section: Par-binding Proteins and Their Functionsmentioning

confidence: 99%

The Enigmatic Function of PARP1: From PARylation Activity to PAR Readers

Kamaletdinova

Fanaei-Kahrani

Wang

2019

Cells

111

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Poly(ADP-ribosyl)ation (PARylation) is catalysed by poly(ADP-ribose) polymerases (PARPs, also known as ARTDs) and then rapidly removed by degrading enzymes. Poly(ADP-ribose) (PAR) is produced from PARylation and provides a delicate and spatiotemporal interaction scaffold for numerous target proteins. The PARylation system, consisting of PAR synthesizers and erasers and PAR itself and readers, plays diverse roles in the DNA damage response (DDR), DNA repair, transcription, replication, chromatin remodeling, metabolism, and cell death. Despite great efforts by scientists in biochemistry, cell and molecular biology, genetics, and pharmacology over the last five decades, the biology of PARPs and PARylation remains enigmatic. In this review, we summarize the current understanding of the biological function of PARP1 (ARTD1), the founding member of the PARP family, focusing on the inter-dependent or -independent nature of different functional domains of the PARP1 protein. We also discuss the readers of PAR, whose function may transduce signals and coordinate the cellular processes, which has recently emerged as a new research avenue for PARP biology. We aim to provide some perspective on how future research might disentangle the biology of PARylation by dissecting the structural and functional relationship of PARP1, a major effector of the PARPs family.

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“…Although the Wnt/β-catenin pathway shows many benefits, its dysregulation causes extensive diseases, such as cancer, cardiovascular disease and renal disease [5][6][7][8][9]. Many biological antibodies and chemotherapeutic reagents targeting the aberrant Wnt/β-catenin signaling have been developed, some of which are in different clinical trials [9][10][11][12][13][14][15][16][17]. However, side effects and resistance of biological antibodies as well as chemotherapeutic reagents are frequently observed in clinical trials, which severely restrict their use.…”

Section: Introductionmentioning

confidence: 99%