A protein tertiary structure mimetic modulator of the Hippo signalling pathway

Adihou H, Gopalakrishnan R, Förster T, Guéret SM, Gasper R, Geschwindner S, Carrillo García C, Karatas H, Pobbati AV, Vazquez-Chantada M, Davey P, Wassvik CM, Pang JKS, Soh BS, Hong W, Chiarparin E, Schade D, Plowright AT, Valeur E, Lemurell M, Grossmann TN, Waldmann H. (2020) Nat Commun


The therapeutic regulation of gene transcription is a long-standing goal in pharmaceutical research. Transcription factors, proteins with key roles in this process, mediate their function mainly by protein-protein interactions, which makes them challenging targets. In a unique collaboration of academia and pharmaceutical industry scientists from AstraZeneca, the Vrije Universiteit (VU) Amsterdam and the Max Planck Institute of Molecular Physiology in Dortmund (MPI) have now developed a protein tertiary structure mimetic capable of inhibiting the interaction of the transcription factor (TF) TEAD with its co-repressor VGL4 and thereby activating proliferation via the Hippo pathway.

Proteomimetic binds to the transcription factor TEAD and thereby activates transcription of TEAD target genes of the Hippo signaling pathway
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