Figure 1. AR structural domains, comparison with AR splice variants and the predicted effect of taxane treatment on AR splice variant nuclear localization.

AR-FL associates with microtubules and uses them as tracks for ligand-induced nuclear translocation. Taxane treatment inhibits AR-FL nuclear accumulation and activity downstream of microtubule stabilization (13, 41). AR-FL binds microtubules via its hinge domain, which is retained in AR^v567es but absent in AR-V7 (12). Taxane treatment inhibits microtubule dynamics and is predicted to differentially affect the nuclear localization of each variant as follows: AR-FL is kept inactive in the cytoplasm (top right); AR-V7 nuclear localization is unaffected, due to the hinge-less AR-V7 association with MTs (middle right); and AR^v567es nuclear localization is partially impaired (bottom right). The latter is due to the fact that the entire C-terminal AR domain (exons 2–8) mediates maximal MT association (AR-FL), while the hinge domain (present in AR^v567es), is the minimum functional domain required for MT binding, albeit not as extensively as the entire C-terminus (12).

AR, androgen receptor; CE, cryptic exon; DBD, DNA-binding domain; FL, full length; LBD, ligand-binding domain; NTD, N-terminal domain; MT, microtubule.