Figure 2.

Schematic of the proteolytic pathways of ATN1. ATN1 is synthesized in the cytoplasm and translocates to the nucleus where it is proteolytically cleaved. Misfolded ATN1s are targets of proteasomal degradation. After importation into the nucleus, the full-length ATN1 was independently cleaved into two fragments. One fragment stayed within the nuclear matrix and executed its function on the nuclear matrix and was regulated by zinc-dependent metal-loprotease [22]. The other was exported to the cytoplasm and assembled in the cytoplasmic organelle. Caspases were directly involved in the cleavage of the latter fragment and regulated the accumulation of the fragment in the cytoplasm. Z-VAD-FMK, an inhibitor of caspase activity, accelerated the accumulation of the fragment in the cytoplasm.