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Fig. 5. Prostate cancer-related AR-LBD mutants display reduced mobility in the presence of their agonistic ligands. Nuclear mobility of antiandrogen-resistant prostate cancer mutants AR(T877A) and AR(W741C) was investigated using two complementary FRAP assays (see also Fig. 2): strip-FRAP (A,C,E) and combined FLIP and FRAP (B,D,F). Intranuclear mobility of these mutants in the presence of 10–9 M R1881 (A,B), 10–6 M OH-flutamide (C,D) or 10–6 M bicalutamide (E,F) was studied. Mobility of non-DNA-binding GFP-AR(A573D) is plotted as a reference. Experimental settings were identical to those described in Fig. 2. Lower graphs in C-F show computer simulations corresponding to the average of best fits of strip-FRAP and FLIP-FRAP models (data in Table 1) of the experimental curves of GFP-AR(T877A) (C,D) and GFP-AR(W741C) in the presence of 1 µM OH-flutamide (C,D) or bicalutamide (E,F). Absolute values of the residuals of computer-simulated curves and experimental data are plotted below the x-axis.





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