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Multi-model functionalization of disease-associated PTEN missense mutations identifies multiple molecular mechanisms underlying protein dysfunction

Mutations in PTEN have been associated with various human disease, including autism spectrum disorder (ASD) and cancer. Here, the authors assess the function of 106 PTEN variants in yeast, invertebrate models and cell culture and report that PTEN variants generally decrease protein stability.

Kathryn L. Post
Manuel Belmadani
Kurt Haas
ResearchOpen Access29 Apr 2020
Nature Communications

Volume: 11, P: 1-16
Author Correction: DCAF1-based PROTACs with activity against clinically validated targets overcoming intrinsic- and acquired-degrader resistance

Martin Schröder
Martin Renatus
Claudio R. Thoma
Amendments and CorrectionsOpen Access19 Aug 2024
Nature Communications

Volume: 15, P: 1-5
DCAF1-based PROTACs with activity against clinically validated targets overcoming intrinsic- and acquired-degrader resistance

Targeted protein degradation (TPD) is a key modality for drug discovery. Here the authors present the discovery and analysis of reversible DCAF1-PROTACs, which show efficacy in cellular environments resistant to VHL-PROTACs or with acquired resistance to CRBN-PROTACs.

Martin Schröder
Martin Renatus
Claudio R. Thoma
ResearchOpen Access04 Jan 2024
Nature Communications

Volume: 15, P: 1-19
Structure of the MRAS–SHOC2–PP1C phosphatase complex

A structure of the MRAS–SHOC2–PP1C complex supports a RAS-driven and multi-molecular model for RAF activation in which individual RAS–GTP molecules recruit RAF–14-3-3 and SHOC2–PP1C to activate the downstream pathway.

Zachary J. Hauseman
Michelle Fodor
Daniel A. King
ResearchOpen Access13 Jul 2022
Nature

Volume: 609, P: 416-423
Protein destabilization underlies pathogenic missense mutations in ARID1B

Using deep mutational scanning, the authors uncover the functional consequence of missense mutations in ARID1B, a subunit of the SWI/SNF chromatin remodeling complex that is frequently mutated in human Coffin–Siris syndrome and in cancer.

Fanny Mermet-Meillon
Samuele Mercan
Giorgio G. Galli
ResearchOpen Access12 Feb 2024
Nature Structural & Molecular Biology

Volume: 31, P: 1018-1022

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Multi-model functionalization of disease-associated PTEN missense mutations identifies multiple molecular mechanisms underlying protein dysfunction

Author Correction: DCAF1-based PROTACs with activity against clinically validated targets overcoming intrinsic- and acquired-degrader resistance

DCAF1-based PROTACs with activity against clinically validated targets overcoming intrinsic- and acquired-degrader resistance

Structure of the MRAS–SHOC2–PP1C phosphatase complex

Protein destabilization underlies pathogenic missense mutations in ARID1B

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