Parkin: an Extremely Versatile E3 Ubiquitin Ligase
10.13865/j.cnki.cjbmb.2020.12.1354
- Author:
Chen-Yue ZHU
1
;
Xi-Xia YUAN
1
;
Tie-Song LI
1
Author Information
1. College of Life Sciences, Lamprey Research Center, Key Laboratory of Liaoning Provincial Biotechnology and Drug Discovery, Liaoning Normal University
- Publication Type:Journal Article
- Keywords:
cancer;
E3 ubiquitin ligase;
Parkin;
Parkinson's disease (PD);
Parkinson's disease gene 2(PARK2)
- From:
Chinese Journal of Biochemistry and Molecular Biology
2021;37(3):289-299
- CountryChina
- Language:Chinese
-
Abstract:
Parkin, also known as PARK2, has been closely related to Parkinson's disease (PD) since its discovery. It is considered to be a neuroprotective gene. With the in-depth understanding for its structure, Parkin has been unveiled as an E3 ubiquitin ligase. Parkin is involved in the regulation of cell cycle, mitochondrial homeostasis, energy metabolism and other cellular processes, and is closely related to many diseases. It even plays completely opposite roles in the same pathway, namely cell proliferation and apoptosis, indicating that this must be a gene with an extremely broad and important role. This article summarizes the discovery and structure of Parkin and its self-inhibiting characteristics, focusing on the ubiquitination process that it participates in as E3 ubiquitin ligase and the resulting autophagy, protein degradation, changes in protein subcellular localization and protein interaction. These may all serve as the basis for Parkin to prevent PD and suppress tumors. On this basis, two reasons for Parkin abnormalities leading to PD are summarized: abnormal protein quality control and mitochondrial dysfunction, and extended to cardiovascular and kidney diseases caused by the abnormality of Parkin due to mitochondrial dysfunction. The internal connection between Parkin and cancer is also introduced from the aspects of Parkin as a tumor suppressor, regulating cell cycle, apoptosis and metastasis, oxidative stress and energy metabolism. By maintaining the active state of Parkin or enhancing its expression, it may be possible to improve the condition of PD patients. But the mechanism of Parkin's inhibition of tumor growth remains to be deciphered, and the potential role of Parkin in mediating the relationship between PD and cancer risk should be strengthened. These follow-up in-depth studies and their role in the diagnosis and treatment of related diseases and application of target molecules laid the foundation.
