Regulation of Proto-Dbl through the Ubox Domain of CHIP
MetadataShow full item record
The Dbl protein is a product of a proto-oncogene that functions as a guanine nucleotide exchange factor for Rho-family GTPases. It is responsible for activating the GTPases by facilitating the dissociation of GDP thus allowing for the binding of GTP. Intracellular levels of Dbl are regulated by ubiquitin-mediated proteolysis. CHIP is the E3 protein-ubiquitin ligase responsible for this ubiquitination. More specifically, the Ubox domain of CHIP is critical to this interaction. Oncogenic Dbl, which lacks its spectrin domain, cannot bind CHIP and therefore escapes degradation. This causes accumulation of the oncogene product in the cell, and leads to persistent activation of its downstream pathways.
dissertation or thesis