RHOB: Ras homolog gene family, member B
PDB Code: 2FV8
Cells respond in many ways to environmental changes including altering gene expression, physically moving locations, changes to cell-cell interactions, differentiation and even altering their life spans. This is achieved through a signalling network that consists of several signalling pathways. The network receives multiple signals, interprets the signals, amplifies and then transmits the signals. One of the best characterised signalling pathways involves the ras GTPase family. The importance of this family of small GTPases to human health was first recognised through the identification of the human H-Ras, N-Ras and K-Ras genes as being oncogenic.
The family of Rho GTPases are involved in cell motility and proliferation through the reorganisation of actin and vesicle trafficking. RHOB is localised mainly to early endosomes and, in contrast to its closely related family member RHOA, functions as a tumor suppressor.
Post-translational modification (PTM) of the small GTPase family members is an important process that defines the cellular location and function of the enzymes. Targeting of the membrane localisation PTM via knockout of the lipid addition with particularly emphasis on the first step involving farnesyltransferase appears to be promising. Originally it was believed that the Ras family members of small GTPases were the targets however RHOB maybe the true target . Phase II and III clinical trials have shown activity of FTIs against selective malignancies.
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