Substitutions in general translation initiation factor eIF1A found as recurring somatic mutations in uveal melanoma destabilize the closed conformation of the preinitiation complex at the start codon and increase discrimination against suboptimal initiation codons genome-wide.
Combining powerful simulation methods uncovers the structural and dynamical changes driving G protein activation in atomic detail, revealing the allosteric network that triggers GDP release and reconciling diverse experimental data.
Treatment with precision nanomedicine in combination with an anti-angiogenic peptide enhance anti-tumor efficacy while minimizing toxicities in a pre-clinical glioblastoma model, making this approach a promising and important therapeutic alternative for patients.
The Ras activator RasGRP1 that impacts Ras signals in immune cells, leukemias, and colorectal cancer, switches to an active conformation aided by a pH-sensitive histidine residue in a central location of the RasGRP1 molecule.
Loss of BAP1 function is associated with increased sensitivity to TRAIL and other death receptor agonists in malignant mesothelioma, where this is a frequent event, with immediate and actionable therapeutic implications.