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

BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE

卷:1822

Article

Chen, Yvan²  Fang, Shang-Ting¹  Yeh, Pei-Chi²  Yang, Hsueh-Hui^3,4  Chen, Shin-Yuan⁵  Chang, Chih-Jui⁶  Zhai, Wei-Jun³  Chen, Yi Cheng^1,2  Juang, Yue-Li^2,7 

[1] Mackay Med Coll, Dept Med, New Taipei City 252, Taipei County, Taiwan

[2] Tzu Chi Univ, Inst Med Sci, Hualien 970, Taiwan

[3] Buddhist Tzu Chi Gen Hosp, Dept Med Res, Hualien 970, Taiwan

[4] Tzu Chi Coll Technol, Gen Educ Ctr, Hualien 970, Taiwan

[5] Buddhist Tzu Chi Gen Hosp, Dept Neurosurg, Hualien 970, Taiwan

[6] Tzu Chi Univ, Inst Mol Biol & Human Genet, Hualien 970, Taiwan

[7] Tzu Chi Univ, Inst Microbiol Immunol & Biochem, Hualien 970, Taiwan

关键词: PARK2;    Mitosis;    Centrosome;    Spindle assembly checkpoint;    Self-interaction;   

DOI  :  10.1016/j.bbadis.2011.12.007

来源: Elsevier

【 摘 要 】

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. (C) 2011 Elsevier B.V. All rights reserved.

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