RhoBTB proteins in cancer

The most peculiar members of the Rho GTPase family are the RhoBTB proteins - large, multimodular proteins that contain two copies of the BTB protein-protein interaction module. While we know very little of the signalling pathways controlled by RhoBTBs, they are some of the oldest members of the family, predating RhoA and Cdc42. While other Rho GTPase may have critical enabling roles in cancer, the RhoBTBs show the clearest evidence for genetic alteration - with loss, mutation, and silencing of the RhoBTB2 isoform being a seemingly common event in a wide range of carcinomas. While activation of other Rho GTPase pathways can promote invasion and metastasis, the RhoBTBs appear to have a protective role and may function as tumour suppressors.