scholarly journals Linear ubiquitin chains: enzymes, mechanisms and biology

Open Biology ◽  
2017 ◽  
Vol 7 (4) ◽  
pp. 170026 ◽  
Author(s):  
Katrin Rittinger ◽  
Fumiyo Ikeda
Keyword(s):  
Cellular Response ◽  
Apoptotic Cell ◽  
Gene Mutations ◽  
E3 Ligase ◽  
Biological Functions ◽  
Post Translational Modification ◽  
Ubiquitin Chain ◽  
Polyubiquitin Chains ◽  
Ubiquitin E3 Ligase ◽  
Ubiquitin Receptors

Ubiquitination is a versatile post-translational modification that regulates a multitude of cellular processes. Its versatility is based on the ability of ubiquitin to form multiple types of polyubiquitin chains, which are recognized by specific ubiquitin receptors to induce the required cellular response. Linear ubiquitin chains are linked through Met 1 and have been established as important players of inflammatory signalling and apoptotic cell death. These chains are generated by a ubiquitin E3 ligase complex called the linear ubiquitin chain assembly complex (LUBAC) that is thus far the only E3 ligase capable of forming linear ubiquitin chains. The complex consists of three subunits, HOIP, HOIL-1L and SHARPIN, each of which have specific roles in the observed biological functions of LUBAC. Furthermore, LUBAC has been found to be associated with OTULIN and CYLD, deubiquitinases that disassemble linear chains and counterbalance the E3 ligase activity of LUBAC. Gene mutations in HOIP, HOIL-1L and OTULIN are found in human patients who suffer from autoimmune diseases, and HOIL-1L mutations are also found in myopathy patients. In this paper, we discuss the mechanisms of linear ubiquitin chain generation and disassembly by their respective enzymes and review our current understanding of their biological functions and association with human diseases.

scholarly journals HTLV-1 Tax Functions as a Ubiquitin E3 Ligase for Direct IKK Activation via Synthesis of Mixed-Linkage Polyubiquitin Chains

2016 ◽  
Vol 12 (4) ◽  
pp. e1005584 ◽  
Author(s):  
Chong Wang ◽  
Wenying Long ◽  
Chao Peng ◽  
Lin Hu ◽  
Qiong Zhang ◽  
...  
Keyword(s):  
E3 Ligase ◽  
Polyubiquitin Chains ◽  
Ubiquitin E3 Ligase

scholarly journals CENP-B dynamics at centromeres is regulated by a SUMOylation/ubiquitination and proteasomal-dependent degradation mechanism involving the SUMO-targeted ubiquitin E3 ligase RNF4

2018 ◽  
Author(s):  
Jhony El Maalouf ◽  
Pascale Texier ◽  
Indri Erliandri ◽  
Camille Cohen ◽  
Armelle Corpet ◽  
...  
Keyword(s):  
Dna Binding ◽  
Degradation Mechanism ◽  
E3 Ligase ◽  
Major Constituent ◽  
Post Translational Modification ◽  
Post Translational Modifications ◽  
Ubiquitin E3 Ligase ◽  
Satellite Repeats ◽  
Histone H3 Variant ◽  
Centromeric Protein

AbstractCentromeric protein B (CENP-B) is a major constituent of the centromere. It is a DNA binding protein that recognizes a specific 17-nt sequence present in the centromeric alphoid satellite repeats. CENP-B importance for centromere stability has only been revealed recently. In addition to its DNA binding properties, CENP-B interacts with the histone H3 variant CENP-A and CENP-C. These interactions confer a mechanical strength to the kinetochore that enables accurate sister chromatids segregation to avoid aneuploidy. Therefore, understanding the mechanisms that regulate CENP-B stability at the centromere is a major unresolved issue for the comprehension of centromere function. In this study, we demonstrate that lysine K402 of CENP-B is a substrate for SUMO post-translational modifications. We show that K402 regulates CENP-B stability at centromeres through a SUMOylation/ubiquitination and proteasomal-dependent degradation mechanism involving the SUMO-Targeted Ubiquitin E3 Ligase RNF4/SNURF. Our study describes SUMOylation of CENP-B as a major post-translational modification involved in centromere dynamics.

scholarly journals HTLV-1 Tax Stimulates Ubiquitin E3 Ligase, Ring Finger Protein 8, to Assemble Lysine 63-Linked Polyubiquitin Chains for TAK1 and IKK Activation

2015 ◽  
Vol 11 (8) ◽  
pp. e1005102 ◽  
Author(s):  
Yik-Khuan Ho ◽  
Huijun Zhi ◽  
Tara Bowlin ◽  
Batsukh Dorjbal ◽  
Subha Philip ◽  
...  
Keyword(s):  
Ring Finger ◽  
E3 Ligase ◽  
Ring Finger Protein ◽  
Polyubiquitin Chains ◽  
Ubiquitin E3 Ligase ◽  
Finger Protein

scholarly journals The ubiquitin E3 ligase activity of BRCA1 and its biological functions

Cell Division ◽  
2008 ◽  
Vol 3 (1) ◽  
pp. 1 ◽  
Author(s):  
Wenwen Wu ◽  
Ayaka Koike ◽  
Takashi Takeshita ◽  
Tomohiko Ohta
Keyword(s):  
E3 Ligase ◽  
Biological Functions ◽  
Ubiquitin E3 Ligase

scholarly journals Ub-clipping: an approach for studying ubiquitin chain architecture

2019 ◽  
Author(s):  
Kirby N. Swatek ◽  
Joanne L. Usher ◽  
Anja F. Kueck ◽  
Christina Gladkova ◽  
Tycho E.T. Mevissen ◽  
...  
Keyword(s):  
New Technology ◽  
Cellular Biology ◽  
Post Translational Modification ◽  
Viral Protease ◽  
Ubiquitin Chain ◽  
Polyubiquitin Chains ◽  
Chain Architecture ◽  
Insight Into ◽  
Shed Light ◽  
Tools And Methods

Abstract The post-translational modification of proteins with ubiquitin is a dynamic multifaceted process affecting all aspects of eukaryotic cellular biology. The complexity of ubiquitin modifications arises from their ability to form architecturally distinct polyubiquitin chains1-3. Despite our understanding of the importance of these signals, we currently lack tools and methods to study them. Here we describe an approach, termed Ub-clipping, which provides unprecedented insight into ubiquitin chain architecture. This protocol is related to our recent Nature paper titled, “Insights into ubiquitin chain architecture using Ub-clipping”. This technology takes advantage of an engineered viral protease, Lbpro*, which ‘clips’ ubiquitin such that the information on the site of modification is retained and the remaining ubiquitin and substrate polypeptides are kept intact. The goal of this protocol is to allow researchers to efficiently adapt our new technology to their proteomic workflows. We anticipate this method will continue to shed light on the architecture of ubiquitin signals, and therefore further our understanding of the ubiquitin code across a broad spectrum of biological systems.

scholarly journals Structural Diversity of Ubiquitin E3 Ligase

Molecules ◽  
2021 ◽  
Vol 26 (21) ◽  
pp. 6682
Author(s):  
Sachiko Toma-Fukai ◽  
Toshiyuki Shimizu
Keyword(s):  
E3 Ligase ◽  
Structural Diversity ◽  
Biological Processes ◽  
Post Translational Modification ◽  
Post Translational Modifications ◽  
E3 Ligases ◽  
Cellular Processes ◽  
Ubiquitin E3 Ligase ◽  
Ubiquitin Ligase E3 ◽  
Ubiquitin Conjugating Enzyme

The post-translational modification of proteins regulates many biological processes. Their dysfunction relates to diseases. Ubiquitination is one of the post-translational modifications that target lysine residue and regulate many cellular processes. Three enzymes are required for achieving the ubiquitination reaction: ubiquitin-activating enzyme (E1), ubiquitin-conjugating enzyme (E2), and ubiquitin ligase (E3). E3s play a pivotal role in selecting substrates. Many structural studies have been conducted to reveal the molecular mechanism of the ubiquitination reaction. Recently, the structure of PCAF_N, a newly categorized E3 ligase, was reported. We present a review of the recent progress toward the structural understanding of E3 ligases.

scholarly journals Nedd4 E3 ligase and beta-arrestins regulate ubiquitination, trafficking, and stability of the mGlu7 receptor

eLife ◽  
2019 ◽  
Vol 8 ◽  
Author(s):  
Sanghyeon Lee ◽  
Sunha Park ◽  
Hyojin Lee ◽  
Seulki Han ◽  
Jae-man Song ◽  
...  
Keyword(s):  
Metabotropic Glutamate Receptor ◽  
E3 Ligase ◽  
Ubiquitin Proteasome System ◽  
Surface Expression ◽  
Degradation Pathway ◽  
Mapk Signaling ◽  
Post Translational Modification ◽  
Excitatory Neurotransmitter ◽  
Ubiquitin E3 Ligase ◽  
And Function

The metabotropic glutamate receptor 7 (mGlu7) is a class C G protein-coupled receptor that modulates excitatory neurotransmitter release at the presynaptic active zone. Although post-translational modification of cellular proteins with ubiquitin is a key molecular mechanism governing protein degradation and function, mGlu7 ubiquitination and its functional consequences have not been elucidated yet. Here, we report that Nedd4 ubiquitin E3 ligase and β-arrestins regulate ubiquitination of mGlu7 in heterologous cells and rat neurons. Upon agonist stimulation, β-arrestins recruit Nedd4 to mGlu7 and facilitate Nedd4-mediated ubiquitination of mGlu7. Nedd4 and β-arrestins regulate constitutive and agonist-induced endocytosis of mGlu7 and are required for mGlu7-dependent MAPK signaling in neurons. In addition, Nedd4-mediated ubiquitination results in the degradation of mGlu7 by both the ubiquitin-proteasome system and the lysosomal degradation pathway. These findings provide a model in which Nedd4 and β-arrestin act together as a complex to regulate mGlu7 surface expression and function at presynaptic terminals.

scholarly journals Nedd4 E3 ligase and beta-arrestins regulate ubiquitination, trafficking, and stability of the mGlu7 receptor

2019 ◽  
Author(s):  
Sanghyeon Lee ◽  
Sunha Park ◽  
Hyojin Lee ◽  
Seulki Han ◽  
Jae-man Song ◽  
...  
Keyword(s):  
Metabotropic Glutamate Receptor ◽  
E3 Ligase ◽  
Surface Expression ◽  
Mapk Signaling ◽  
Post Translational Modification ◽  
Excitatory Neurotransmitter ◽  
Metabotropic Glutamate ◽  
Ubiquitin E3 Ligase ◽  
Beta Arrestins ◽  
And Function

AbstractThe metabotropic glutamate receptor 7 (mGlu7) is a class C G protein-coupled receptor (GPCR) that modulates excitatory neurotransmitter release at the presynaptic active zone. Although post-translational modification of cellular proteins with ubiquitin is a key molecular mechanism governing protein degradation and function, mGlu7 ubiquitination and its functional consequences have not been elucidated yet. Here, we report that Nedd4 ubiquitin E3 ligase and β-arrestins regulate ubiquitination of mGlu7 in heterologous cells and neurons. Upon agonist-stimulation, β-arrestins recruit Nedd4 to mGlu7 and facilitate Nedd4-mediated ubiquitination of mGlu7. Nedd4 and β-arrestins regulate constitutive and agonist-induced endocytosis of mGlu7 and are required for mGlu7-dependent MAPK signaling in neurons. In addition, Nedd4-mediated ubiquitination results in the degradation of mGlu7 by both the lysosomal and proteasomal degradation pathways. These findings provide a model in which Nedd4 and β-arrestin act together as a complex to regulate mGlu7 surface expression and function at the presynaptic terminals.

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