Differences in the regulation of K-Ras and H-Ras isoforms by monoubiquitination

Background: Ras proteins are critical regulators of cellular growth and are differentially modified by ubiquitination. Results: Chemical ubiquitination and immunoprecipitation assays demonstrate that monoubiquitination causes sustained H-Ras activation in the absence of oncogenic mutations. Conclusion: The mechanism by which H-Ras is activated by monoubiquitination is both isoform-specific and site-specific. Significance: Monoubiquitination adds a new level of regulation and complexity to isoform-specific Ras signaling.