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

2019 ◽  
Author(s):  
Nathalie Sans
Keyword(s):  
E3 Ligase ◽  
Beta Arrestins

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.

scholarly journals Author response: 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):  
E3 Ligase ◽  
Author Response ◽  
Beta Arrestins

A Caged E3 Ligase Ligand for PROTAC-Mediated Protein Degradation with Light

2019 ◽  
Author(s):  
Cyrille Kounde ◽  
Maria M. Shchepinova ◽  
Edward Tate
Keyword(s):  
Protein Degradation ◽  
Irradiation Time ◽  
E3 Ligase ◽  
Von Hippel Lindau ◽  
Short Irradiation ◽  
Short Irradiation Time ◽  
Spatiotemporal Control

A caging group has been appended to a widely used Von Hippel Lindau (VHL) E3 ligase ligand for targeted protein degradation with PROTACs. Proteolysis is triggered only after a short irradiation time allowing spatiotemporal control of the protein’s fate.

From Inhibition to Degradation: Targeting the Anti-apoptotic Protein Myeloid Cell Leukemia 1(MCL1)

2019 ◽  
Author(s):  
James Papatzimas ◽  
Evgueni Gorobets ◽  
Ranjan Maity ◽  
Mir Ishruna Muniyat ◽  
Justin L. MacCallum ◽  
...  
Keyword(s):  
Small Molecules ◽  
E3 Ligase ◽  
Myeloid Cell ◽  
Cell Leukemia ◽  
New Class ◽  
Apoptotic Protein ◽  
Family Protein ◽  
Ubiquitination Pathway

<div> <div> <div> <p>Here we show the development of heterobifunctional small molecules capable of selectively targeting MCL1 using a Proteolysis Targeting Chimera (PROTAC) methodology leading to successful degradation. We have confirmed the involvement of the E3 ligase CUL4A-DDB1 cereblon (CRBN) ubiquitination pathway, making these PROTACs a first step toward a new class of anti-apoptotic BCL-2 family protein degraders. </p> </div> </div> </div>

PHOTACs Enable Optical Control of Protein Degradation

2019 ◽  
Author(s):  
Martin Reynders ◽  
Bryan Matsuura ◽  
Marleen Bérouti ◽  
Daniele Simoneschi ◽  
Antonio Marzio ◽  
...  
Keyword(s):  
Protein Degradation ◽  
E3 Ligase ◽  
Optical Control ◽  
Cellular Proteins ◽  
Bifunctional Molecules ◽  
Protein Levels ◽  
Lead Compounds ◽  
Subsequent Degradation ◽  
Temporal And Spatial ◽  
Precision Therapeutics

<p><i>PROTACs (proteolysis targeting chimeras) are bifunctional molecules that tag proteins for ubiquitylation by an E3 ligase complex and subsequent degradation by the proteasome. They have emerged as powerful tools to control the levels of specific cellular proteins and are on the verge of being clinically used. We now introduce photoswitchable PROTACs that can be activated with the temporal and spatial precision that light provides. These trifunctional molecules, which we named PHOTACs, consist of a ligand for an E3 ligase, a photoswitch, and a ligand for a protein of interest. We demonstrate this concept by using PHOTACs that target either BET family proteins (BRD2,3,4) or FKBP12. Our lead compounds display little or no activity in the dark but can be reversibly activated to varying degrees with different wavelengths of light. Our modular and generalizable approach provides a method for the optical control of protein levels with photopharmacology and could lead to new types of precision therapeutics that avoid undesired systemic toxicity.</i><b></b></p>

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