Degrons are short amino acid sequences that can facilitate the degradation of protein substrates. They can be classified as either ubiquitin-dependent or -independent based on their interactions with the ubiquitin proteasome system (UPS). These amino acid sequences are often found in exposed regions of proteins serving as either a tethering point for an interaction with an E3 ligase or initiating signaling for the direct degradation of the protein. Recent advancements in the protein degradation field have shown the therapeutic potential of both classes of degrons through leveraging their degradative effects to engage specific protein targets. This review explores what targeted protein degradation applications degrons can be used in and how they have inspired new degrader technology to target a wide variety of protein substrates.
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http://dx.doi.org/10.1039/d4md00787e | DOI Listing |
J Integr Plant Biol
January 2025
Key Laboratory of National Forestry and Grassland Administration on Plant Conservation and Utilization in Southern China & Guangdong Provincial Key Laboratory of Applied Botany, South China Botanical Garden, Chinese Academy of Sciences, Guangzhou, 510650, China.
Reactive oxygen species (ROS) plays critical roles in modulating plant growth and stress response and its homeostasis is fine tuned using multiple peroxidases. HO, a major kind of ROS, is removed rapidly and directly using three catalases, CAT1, CAT2, and CAT3, in Arabidopsis. Although the activity regulations of catalases have been well studied, their degradation pathway is less clear.
View Article and Find Full Text PDFJ Med Chem
January 2025
Department of Chemical and Systems Biology, Stanford Cancer Institute, School of Medicine Stanford University, Stanford, California 94305-6104, United States.
Molecular glue degraders (MGDs) are small molecules that facilitate proximity between a target protein and an E3 ubiquitin ligase, thereby inducing target protein degradation. Glutarimide-containing compounds are MGDs that bind cereblon (CRBN) and recruit neosubstrates. Through explorative synthesis of a glutarimide-based library, we discovered a series of molecules that induce casein kinase 1 alpha (CK1α) degradation.
View Article and Find Full Text PDFJ Dent Sci
January 2025
Department of Oral Medicine, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Background/purpose: Oral lichen planus (OLP) is a chronic inflammatory disorder characterized by basement membrane disruption, which plays a crucial role in its pathogenesis. Matrix metalloproteinases (MMPs), a group of proteolytic enzymes, contribute to the degradation of the basement membrane. The specific MMPs secreted by keratinocytes in OLP lesions and relevant regulatory mechanisms are not fully understood.
View Article and Find Full Text PDFFront Cell Infect Microbiol
January 2025
Guangxi Key Laboratory for Polysaccharide Materials and Modifications, School of Marine Sciences and Biotechnology, Guangxi Minzu University, Nanning, Guangxi, China.
Interferon regulatory factor 7 (IRF7)-mediated type I interferon antiviral response is crucial for regulating the host following viral infection in chickens. Infectious bursal disease virus (IBDV) is a double-stranded RNA virus that induces immune suppression and high mortality rates in chickens aged 3-6 weeks. Previous studies have shown that IBDV infection antagonizes the type I interferon production to facilitate viral replication in the cell, and IRF7 signaling might play an important role.
View Article and Find Full Text PDFBio Protoc
January 2025
Department of Structural Interactomics, Leibniz-Forschungsinstitut für Molekulare Pharmakologie (FMP), Berlin, Germany.
Neurons communicate through neurotransmission at highly specialized junctions called synapses. Each neuron forms numerous synaptic connections, consisting of presynaptic and postsynaptic terminals. Upon the arrival of an action potential, neurotransmitters are released from the presynaptic site and diffuse across the synaptic cleft to bind specialized receptors at the postsynaptic terminal.
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