Article

Oncogenic PI3Kα variants reveal graded conformational spectrum with mutation-specific cryptic pockets

2025-06-29

Abstract excerpt

Cancer-prone alleles exhibit single hotspot mutations. However, the combination of a cancer hotspot and a weak or moderate mutation (the ‘one-two punch’ hypothesis) produces same-allele double variants with a significantly different and potentially graded clinical phenotypic spectrum. Oncogenic PI3Kα variants, which are also associated with benign tumors and neurodevelopmental disorders, offer statistical support...

Topics

Open a Topic to create a Post that cites this publication.

Identifiers and source

Literature Corpus work: 4bea94e5-491f-521d-972a-49f908870567
DOI: 10.1101/2025.06.26.661751

Open publication

Related research

Semantic proximity does not establish scientific evidence.

Click a neighbor to travelStep 1 · 12 closest

Oncogenic PI3Kα variants reveal graded conformational spectrum with mutation-specific cryptic pocketsDOI 10.1101/2025.06.26.661751Read

PI3K Driver Mutations: A Biophysical Membrane-Centric Perspective.Semantic proximity Read

Targeting SHP2 Cryptic Allosteric Sites for Effective Cancer Therapy.Semantic proximity Read

Oncogenic mutations of PIK3CA lead to increased membrane recruitment driven by reorientation of the ABD, p85 and C-terminus.Semantic proximity Read

The Landscape of Atypical and Eukaryotic Protein Kinases.Semantic proximity Read

SHP2 clinical phenotype, cancer, or RASopathies, can be predicted by mutant conformational propensities.Semantic proximity Read

Somatic mutations in PI3Kα: Structural basis for enzyme activation and drug designSemantic proximity Read

Structural effects of oncogenic PI3Kα mutations.Semantic proximity Read

Cancer hotspot mutations rewire ERK2 specificity by selective exclusion of docking interactions.Semantic proximity Read

Oncogenic mutations mimic and enhance dynamic events in the natural activation of phosphoinositide 3-kinase p110α (PIK3CA).Semantic proximity Read

Widespread alteration of protein autoinhibition in human cancersSemantic proximity Read

Comprehensive characterization of protein-protein interaction network perturbations by human disease mutationsSemantic proximity Read

HUMAN KINASES DISPLAY MUTATIONAL HOTSPOTS AT COGNATE POSITIONS WITHIN CANCER.Semantic proximity Read