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.
Institute of Medical Sciences, Tzu-Chi University, Hualien 970, Taiwan.
Yvan
Y
Chen
Shang-Ting
ST
Fang
Pei-Chi
PC
Yeh
Hsueh-Hui
HH
Yang
Shin-Yuan
SY
Chen
Chih-Jui
CJ
Chang
Wei-Jun
WJ
Zhai
Yi Cheng
YC
Chen
Yue-Li
YL
Juang
D015153:Blotting, Western; D002942:Circular Dichroism; D006367:HeLa Cells; D006801:Humans; D008856:Microscopy, Fluorescence; D012995:Solubility; D008941:Spindle Apparatus; D044767:Ubiquitin-Protein Ligases / Q000737:chemistry / Q000502:physiology*
D044767:Ubiquitin-Protein Ligases; C111567:parkin protein