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Article

Mutational scanning reveals substrate-assisted autoregulation of the WNT destruction complex.

Nature genetics - 1 Jul 2026

Padmanarayana Murugesh, Sakalas Saira, Sarkar Parijat, Ma Mengxiao, Garvin Ethan R, Lee Ethan, Corsello Steven M, Guettler Sebastian, Pusapati Ganesh V, Rohatgi Rajat

Abstract excerpt

The β-catenin destruction complex (BDC) regulates WNT-β-catenin signaling and is a prime therapeutic target in colorectal cancer, yet its biochemical complexity has hindered mechanistic understanding. We mapped the sequence-function landscape of the BDC using tiled base editor screens across its components CTNNB1, AXIN1, APC and GSK3B. Amongst ~150 previously unreported mutations that affected WNT signaling, we...

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Share to Adenomatous Polyposis Coli Protein
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Methodology Data sources Editorial policy Privacy About Contact Helena Bioinformatics

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Source

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Identifiers

PMID: 42393221
DOI: 10.1038/s41588-026-02662-3
PMCID: PMC13364647

Genes

APC
AXIN1
CTNNB1
GSK3B

Provenance

PubMed metadata and Literature Corpus relationships. Corpus snapshot updated 1 Sept 2026.

Related research

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Mutational scanning reveals substrate-assisted autoregulation of the WNT destruction complex.PMID 42393221Read ↗

Mutational scanning reveals substrate-assisted autoregulation of the WNT destruction complexSemantic proximity Read ↗

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