Journal ArticleDOI
Ubiquitin Ligases: Structure, Function, and Regulation
Ning Zheng,Nitzan Shabek +1 more
TLDR
Current progress in structure-function studies of ubiquitin ligases as well as exciting new discoveries of novel classes of E3s and diverse substrate recognition mechanisms are summarized.Abstract:
Ubiquitin E3 ligases control every aspect of eukaryotic biology by promoting protein ubiquitination and degradation. At the end of a three-enzyme cascade, ubiquitin ligases mediate the transfer of ubiquitin from an E2 ubiquitin-conjugating enzyme to specific substrate proteins. Early investigations of E3s of the RING (really interesting new gene) and HECT (homologous to the E6AP carboxyl terminus) types shed light on their enzymatic activities, general architectures, and substrate degron-binding modes. Recent studies have provided deeper mechanistic insights into their catalysis, activation, and regulation. In this review, we summarize the current progress in structure-function studies of ubiquitin ligases as well as exciting new discoveries of novel classes of E3s and diverse substrate recognition mechanisms. Our increased understanding of ubiquitin ligase function and regulation has provided the rationale for developing E3-targeting therapeutics for the treatment of human diseases.read more
Citations
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Targeted protein degradation: elements of PROTAC design.
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TL;DR: This review aims to highlight the recent advances in targeted protein degradation and describe the challenges that need to be addressed in order to efficiently develop potent PROTACs.
References
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Journal ArticleDOI
The Ubiquitin System
Avram Hershko,Aaron Ciechanover +1 more
TL;DR: This review discusses recent information on functions and mechanisms of the ubiquitin system and focuses on what the authors know, and would like to know, about the mode of action of ubi...
Journal ArticleDOI
Mutations in the parkin gene cause autosomal recessive juvenile parkinsonism
Tohru Kitada,Shuichi Asakawa,Nobutaka Hattori,Hiroto Matsumine,Yasuhiro Yamamura,Shinsei Minoshima,Masayuki Yokochi,Yoshikuni Mizuno,Nobuyoshi Shimizu +8 more
TL;DR: Mutations in the newly identified gene appear to be responsible for the pathogenesis of Autosomal recessive juvenile parkinsonism, and the protein product is named ‘Parkin’.
Journal ArticleDOI
Mechanisms underlying ubiquitination.
TL;DR: Recent findings reveal that all known E3s utilize one of just two catalytic domains--a HECT domain or a RING finger--and crystal structures have provided the first detailed views of an active site of each type.
Journal ArticleDOI
The Ubiquitin Code
David Komander,Michael Rape +1 more
TL;DR: The structure, assembly, and function of the posttranslational modification with ubiquitin, a process referred to as ubiquitylation, controls almost every process in cells.
Journal ArticleDOI
RING Domain E3 Ubiquitin Ligases
TL;DR: RING E3s have been linked to the control of many cellular processes and to multiple human diseases, and knowledge of the physiological partners, biological functions, substrates, and mechanism of action for most RING E 3s remains at a rudimentary stage.