Biomedical Science Letters (대한의생명과학회지)

The Korean Society for Biomedical Laboratory Sciences (대한의생명과학회)
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Polyubiquitin-Proteasomal Degradation of Leucine-Rich Repeat Kinase 2 Wildtype and G2019S

  • Park, Sangwook (Department of Biomedical Laboratory Science, College of Health and Medical Science, Sangji University)
  • Received : 2021.07.19
  • Accepted : 2021.08.10
  • Published : 2021.09.30
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Abstract

Parkinson disease (PD) is becoming one of the most neurodegenerative disorder worldwide. The deposited aggregates have been connected in the pathophysiology of PD, which are degraded either by ubiquitin-proteasomal system (UPS) or autophagy-lysosomal pathway (ALP). Leucin-rich repeat kinase 2 (LRRK2), one of the neurodegenerative proteins of PD is also stringently controlled by both UPS and ALP degradation as well. However, the polyubiquitination pattern of LRRK2 aggregates is largely unknown. Here, we found that K63-linked polyubiquitinations of G2019S mutant, most familial variant for PD, is highly enhanced compared to those of wild type LRRK2 (WT). In addition, in the presence of overexpressed p62/SQSTM-1, ubiquitination of LRRK2 WT or D1994A was reduced, whereas G2019S mutant was not diminished significantly. Therefore, we propose that degradation of G2019S via UPS is more involved with K63-linked ubiquitination than K48-linked ubiquitination, and overexpressed p62/SQSTM-1 does not enhance degradative effect on G2019S variant.

Keywords

Acknowledgement

This study was supported by the Basic Science Research Program through the National Research Foundation of Korea (NRF) grant (http://ernd.nrf.re.kr) to S.P (NRF-2017R1D1A3B03029902), which was funded by the Ministry of Education.

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