Recent insight into the role of RING-finger E3 ligases in glioma

The ubiquitin proteasome system (UPS) serves as the major posttranslational modification system for the maintenance of protein homeostasis. The ubiquitin ligases (E3s) are responsible for the recognition and recruitment of specific substrate proteins for polyubiquitination. Really interesting new ge...

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Published inBiochemical Society transactions Vol. 49; no. 1; p. 519
Main Authors Cao, Yang, Zhou, Hang, Chen, Xiaoyu, Li, Yin, Hu, Junwen, Zhou, Guoyang, Wang, Lin
Format Journal Article
LanguageEnglish
Published England 26.02.2021
Subjects
Animals
Antineoplastic Agents - pharmacology
Antineoplastic Agents - therapeutic use
Brain Neoplasms - drug therapy
Brain Neoplasms - genetics
Brain Neoplasms - metabolism
Brain Neoplasms - pathology
Glioma - genetics
Glioma - metabolism
Glioma - pathology
Glioma - therapy
Humans
Proteolysis - drug effects
Ubiquitin - metabolism
Ubiquitin-Protein Ligases - physiology
Ubiquitination - genetics
ubiquitin proteasome system
glioma
neddylation
cullin-RING ligases
PROTAC
ring finger E3s
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Summary:The ubiquitin proteasome system (UPS) serves as the major posttranslational modification system for the maintenance of protein homeostasis. The ubiquitin ligases (E3s) are responsible for the recognition and recruitment of specific substrate proteins for polyubiquitination. Really interesting new gene (RING) finger E3s account for the majority of E3s. The human genome encodes more than 600 RING E3s, which are divided into three subclasses: single polypeptide E3s, cullin-RING ligases (CRLs) and other multisubunit E3s. The abnormal regulation of RING E3s has been reported to disrupt normal biological processes and induce the occurrence of many human malignancies. Glioma is the most common type of malignant primary brain tumor. In the last few decades, patient prognosis has improved as novel targeted therapeutic agents have developed. In this review, we will summarize the current knowledge about the dysregulation of RING E3s and the altered stability of their substrates in glioma. We will further introduce and discuss the current status and future perspectives of the application of small inhibitors and proteolysis-targeting chimeric molecules (PROTACs) interfering with RING E3s as potential anticancer agents for glioma.
ISSN:1470-8752
DOI:10.1042/BST20201060