The advent of deep-sequencing techniques has revealed that mutations in G protein–coupled receptor (GPCR) signaling pathways in cancer are more prominent than was previously appreciated. An emergent theme is that cancer-associated mutations tend to cause enhanced GPCR pathway activation to favor oncogenicity. Regulators of G protein signaling (RGS) proteins are critical modulators of GPCR signaling that dampen the activity of heterotrimeric G proteins through their GTPase-accelerating protein (GAP) activity, which is conferred by a conserved domain dubbed the “RGS-box.” Here, we developed an experimental pipeline to systematically assess the mutational landscape of RGS GAPs in cancer. A pan-cancer bioinformatics analysis of the 20 RGS domains with GAP activity revealed hundreds of low-frequency mutations spread throughout the conserved RGS domain structure with a slight enrichment at positions that interface with G proteins. We empirically tested multiple mutations representing all RGS GAP subfamilies and sampling both G protein interface and noninterface positions with a scalable, yeast-based assay. Last, a subset of mutants was validated using G protein activity biosensors in mammalian cells. Our findings reveal that a sizable fraction of RGS protein mutations leads to a loss of function through various mechanisms, including disruption of the G protein–binding interface, loss of protein stability, or allosteric effects on G protein coupling. Moreover, our results also validate a scalable pipeline for the rapid characterization of cancer-associated mutations in RGS proteins.

Adaptation of new high yielding highland rice varieties in Jayawijaya Regency, Papua Province. The research was carried out from June to September 2017 in Jayawijaya, Papua. The aims were to determine the appearance and productivity results of new high yielding rice varieties at an altitude of 1600 m above sea level. The study used a Randomized Block Design and each treatment was repeated 4 times. There were 4 (four) new superior varieties tested and one local variety as a comparison. Inpari 26, Inpari 27, Inpari 28 and Sarinah have been used for the treatment while the comparison variety was existing varieties (local Toraja). Component of growth and a component of production were collected as the parameter. The results showed that the superior variety of Inpari 28 provided the highest adaptability and yield which obtained 4.94 t / ha (MPD) and the age of the pan was also faster than other varieties. It showed the deepest age was obtained by local varieties 190 days after spread.