Impact of Frequent ARID1A Mutations on Protein Stability: Insights into Cancer Pathogenesis.

ABSTRACT: The ARID1A gene, frequently mutated in cancer, encodes the AT-rich interactive domain-containing protein 1A, a key component of the chromatin remodeling SWI/SNF complex. The ARID1A protein features a conserved DNA-binding domain (ARID domain) of approximately 100 residues crucial for its function. Despite the frequency of mutations, the impact on ARID1A's stability and contribution to cancer progression remains unclear. We analyzed five frequent missense mutations R1020S, M1022K, K1047Q, G1063V, and A1089T identified in The Cancer Genome Atlas (TCGA) to assess their effects on the stability of the ARID domain using a hybrid experimental and computational approach. By combining computational stability from web server tools, the structural dynamics from replica exchange discrete molecular si

SUBMITTER: Goutam RK 

PROVIDER: S-EPMC11702796 | biostudies-literature | 2024 Dec

REPOSITORIES: biostudies-literature