Karunaraj, P., Washington, C., Luf, M., Martino-Cortez, Y., Pfleger, C.M. (2024). Characterization of Ras Y4H mutants in Drosophila. MicroPubl Biol 2024(): .
FlyBase ID
FBrf0259066
Publication Type
Research paper
Abstract
Ras signaling plays a highly conserved role from flies to mammals in establishing proper development, and its dysregulation can lead to cancer. In Drosophila , we demonstrated that Ras Tyrosine 4 (Y4) was required for inhibitory ubiquitination by Rabex-5. In humans, rare histidine substitution mutations at Y4 are found in HRas in cerebellar glioblastomas (cGBMs). We report here that analogous Y4H mutations in Drosophila Ras make it less sensitive to Rabex-5-mediated ubiquitination in cells and show increased frequency of vein phenotypes per wing compared to wild-type Ras, which would be consistent with Ras gain-of-function and with their appearance in human cGBMs.
