Abstract
Clinical practice has shown that Parkin is the major causative gene found in an autosomal recessive juvenile parkinsonism (AR-JP) via Parkin mutations and that the Parkin protein is the core expression product of the Parkin gene, which itself belongs to an E3 ubiquitin ligase. Since the discovery of the Parkin gene in the late 1990s, researchers in many countries have begun extensive research on this gene and found that in addition to AR-JP, the Parkin gene is associated with many diseases, including type 2 diabetes, leprosy, Alzheimer’s, autism, and cancer. Recent studies have found that the loss or dysfunction of Parkin has a certain relationship with tumorigenesis. In general, the Parkin gene, a well-established tumor suppressor, is deficient and mutated in a variety of malignancies. Parkin overexpression inhibits tumor cell growth and promotes apoptosis. However, the functions of Parkin in tumorigenesis and its regulatory mechanisms are still not fully understood. This article describes the structure, functions, and post-translational modifications of Parkin, and summarizes the recent advances in the tumor suppressive function of Parkin and its underlying mechanisms.
Highlights
Parkin gene, called PARK2, is located on chromosome 6q25.2-q27, contains 12 exons, and has a length of about 1.5 Mb [1]
Studies have shown that Parkin binds to the ubiquitin-like protein Neural precursor cell-expressed developmentally downregulated 8 (NEDD8) [57], indicating that NEDD8 is linked to Parkin to increase E3 ligase activity by increasing the affinity to E2 ubiquitin ligase Ubiquitin-conjugating Enzyme H8 (UbcH8) and putative substrate aminoacyltransferase p38 subunit, thereby inhibiting the development of the tumor
With in-depth studies on Parkin, it was found that its overexpression inhibits the proliferation of cancer cells, while Parkin’s inactivation promotes the proliferation of cancer cells, demonstrating that Parkin acts as a tumor suppressor [63, 66]
Summary
Called PARK2, is located on chromosome 6q25.2-q27, contains 12 exons, and has a length of about 1.5 Mb [1]. Studies have shown that non-covalent binding of Parkin protein to SUMO-1 enhances Parkin’s nuclear translocation and increases its own ubiquitination, but no significant Parkin protein level difference was detected after the overexpression of SUMO-1, indicating that an increase in autoubiquitination activity does not necessarily result in the protease-dependent degradation of Parkin [48].
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
