The C-terminus of PARK2 is required for its self-interaction, solubility and role in the spindle assembly checkpoint

PARK2, an ubiquitin ligase closely correlated with Parkinson's disease and cancer, has been shown to accumulate at centrosomes to ubiquitinate misfolded proteins accumulated during interphase. In the present study, we demonstrated that PARK2 can also localize to centrosomes in mitosis and that the protein does not fluctuate through the S- to M-phase. A C-terminal truncation of PARK2 resulted in a spindle assembly checkpoint defect, characterized by HeLa cells able to bypass mitotic arrest induced by nocodazole and form multinucleated cells when overexpressing the C-terminal truncated PARK2 protein. The spindle assembly checkpoint defect may be due to a change in a biochemical or structural property of PARK2 caused by the C-terminal truncation, resulting in a loss of self-interaction between PARK2 proteins.

► PARK2 localizes to centrosome and its protein levels do not fluctuate through the cell cycle.
► Ectopic expression of PARK2 C-terminus truncation impairs the mitotic checkpoint and causes cell death.
► Ectopic expression of PARK2ΔC40 causes an accumulation of multinucleated cells.
► PARK2ΔC40 loses the ability of self-interaction, and has reduced solubility and stability.