Conformational transitions in BTG1 antiproliferative protein and their modulation by disease mutants

BTG1 mutation yields supercompetitive B cells primed for malignant transformation

“…S1D]. Q36H and additional BTG1 N-terminal mutations can alter the conformational distribution of BTG1 within the α2-α4 region, as determined by in silico atomistic molecular dynamics simulation ( 31 ).…”

“…Given that BTG1 mutants facilitated translation of MYC and potentially other proteins, we hypothesize that wild-type BTG1 association with MYC mRNAs restricts MYC translation, until reaching a critical T FH cell help strength threshold, whereas mutant BTG1 lowers this threshold through impaired association with MYC mRNAs. These effects are likely mediated through interaction with as of yet unknown RNA binding proteins that might be destabilized by the altered protein conformation induced by mutations such as Q36H ( 31 ). This would confer a partial dominant-negative effect, whereby mutant BTG1 could occupy wild-type BTG1 space, preventing its ability to form functional RNA regulatory complexes while preserving other BTG1 functions.…”

Biophysics of cancer

“…These changes often result in altered or attenuated interactions with interaction partners, and altered interaction networks can lead to the development of cancer. This broad topic is the focus of three excellent papers (7)(8)(9) in this issue of Biophysical Journal. Target identification and the development of biomarkers or anticancer therapies are other active areas of interest for many biophysicists.…”

“…Along these lines, Anne M. Brown and colleagues investigated a potential prognostic marker for an aggressive form of brain cancer, glioblastoma (10). As a foundational work for the future development of therapeutic agents, two papers (8,9) have focused on atomically detailed analyses of the structure and dynamics of cancer-associated proteins (8,9), while a third investigated the molecular mechanism of small-molecule binding to DNA (5).…”