biorxiv.org· Bildik, G., Yang, H., Mao, W., Gannaban, R. B., Bhardwaj, V. K., Uddin, M. N., Jung, S. Y., Pierobon, M., Gomeiz, A., Gorfe, A. A., Hancock, J. F., Marshall, C. B., McCormick, F., Millward, S. W., Liu, J., Bast, R. C., Lu, Z. ·· 16 hours agoPickScore71
DIRAS3 broadly suppresses signaling from diverse oncogenic KRAS hotspot variants through an inhibitory interface
DIRAS3 broadly suppresses signaling from diverse oncogenic KRAS hotspot variants through an inhibitory interface
In brief
A bioRxiv preprint shows that an α5 mimetic of DIRAS3 broadly suppresses MAPK and PI3K signaling driven by multiple KRAS hotspot variants through an inhibitory interface. Immunoprecipitation shows the mimetic reduces KRAS association with RAF1 and p110α in both G12 and Q61 mutants, whereas RMC-7977 inhibits p110α association with Q61 KRAS more weakly.
Why it matters
Structure-function analysis and molecular dynamics membrane topology modeling explain how the DIRAS3 α5 interface inhibits G12 and Q61 KRAS signaling.
Source: biorxiv.org · biorxiv.org