Chemical genetics reveals a role of dCTP pyrophosphatase 1 in Wnt signaling

Friese A, Kapoor S, Schneidewind T, Vidadala SR, Sardana J, Brause A, Förster T, Bischoff M, Wagner J, Janning P, Ziegler S, Waldmann H (2019). Angwandte Chemie

doi: https://doi.org/10.1002/ejoc.201900586

Wnt/𝛃-catenin signaling is essential for normal embryonic development and tissue homeostasis. Its deregulation
plays a crucial role in carcinogenesis. Through a cell-based assay and subsequent target identification and validation the Waldmann lab discovered the pyrrolocoumarin Pyrcoumin, a new competitive inhibitor of dCTP pyrophosphatase 1 (dCTPP1).

Pyrcoumin counteracts the yet unknown interaction of dCTPP1 with ubiquitin carboxyl-terminal hydrolase (USP7). The findings indicate that dCTPP1 plays a role in regulation nof Wnt/𝛃-catenin signaling, which is positivly regulated by the novel inhibitor Pyrcoumin.

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