RhoBTB1 is an unusual Rho GTPase family member. It binds to the Cullin-3 ubiquitin ligase complex via its BTB domains, and is therefore likely to target proteins for proteasomal degradation. We have recently found that it binds via its Rho domain to components of the Rho signalling pathway involved in cell migration. This project will determine the structure of the Rho domain in complex with Rho pathway components, and of the BTB domains with Cullin-3. The function of RhoBTB1 interactions will be investigated in cells by site-directed mutagenesis, high-resolution microscopy and analysis of protein degradation.
Vega F, Fruhwirth G, Ng T, Ridley AJ (2011) RhoA and RhoC have distinct roles in migration and invasion by acting through different targets. J. Cell Biol. 193, 655-665.
Riou P, Kjaer S, Garg R, Purkiss A, George R, Cain RJ, Bineva G, Reymond N, McColl B, Thompson AJ, O’Reilly N, McDonald NQ, Parker PJ, Ridley AJ (2013) 14-3-3 proteins interact with a hybrid prenyl-phosphorylation motif to inhibit G-proteins. Cell 153, 640-653.
RhoC and ROCKs regulate cancer cell interactions with endothelial cells. Reymond N, Im JH, Garg R, Cox S, Soyer M, Riou P, Colomba A, Muschel RJ, Ridley AJ (2015).Mol Oncol S1574-7891(15)00019
Garg, R. Riento, K. Keep, N.H., Morris, J.D.H. and Ridley A.J. (2008). N-terminus-mediated dimerization of ROCK-I is required for RhoE binding and actin reorganization. Biochemical Journal 411, 407-414
22. Garavini, H., Riento, K., Phelan, J.P., McAlister, M.S.B., Ridley, A.J. and Keep, N.H. (2002) Crystal Structure of the Core Domain of RhoE/Rnd3: A Constitutively Activated Small G Protein. Biochemistry 41, 6303 - 6310