FIGURE 2.

The farnesyltransferase inhibitor FTI-276 does not reduce UCH-L1^M in neurons. A, membrane-associated H-ras, but not UCH-L1, is decreased by farnesyltransferase inhibition. Cultured cortical neurons were treated with a DMSO control or increasing amounts of the farnesyltransferase inhibitor FTI-276 (Calbiochem), as indicated, for 48 h and then lysed and subjected to high-speed ultracentrifugation to separate the cytosolic and membrane fractions. Immunoblotting for the known farnesylation substrate H-ras shows an increasing shift from a membrane-associated form to a cytosolic form as the concentration of FTI-276 increases, whereas the proportion of UCH-L1 remains unaffected. B, relative proportions of UCH-L1^M and H-ras^M detected per microgram of protein in the FTI-treated membrane fractions relative to the DMSO control (n = 6 for the DMSO control and 500 nm, and n = 5 for both 1 and 3 μm). Data were analyzed using one-way analysis of variance with post hoc Bonferroni test. *, p < 0.05; **, p < 0.001. a.u., arbitrary units.