The Role of Deubiquitinating Enzymes in Synaptic Function and Nervous System Diseases by Jennifer R. Kowalski, Peter Juo

“…Ubiquitination is a reversible modification mediated by the concerted action of a large number of specific ubiquitin ligases and ubiquitin proteases, called deubiquitinating enzymes (DUBs). …”
Get full text

A multiprotein regulatory module, MED16–MBR1&2, controls MED25 homeostasis during jasmonate signaling by Fangming Wu, Chuanlong Sun, Ziying Zhu, Lei Deng, Feifei Yu, Qi Xie, Chuanyou Li

“…Conversely, two homologous E3 ubiquitin ligases, MED25-BINDING RING-H2 PROTEIN1 (MBR1) and MBR2, negatively regulate JA-responsive gene expression by promoting MED25 degradation. …”
Get full text

FBXL16 Promotes Endometrial Progesterone Resistance via PP2AB55α/Cyclin D1 Axis in Ishikawa by Haoen Liu, Li Han, Liyan Zhong, Xiaodan Zhuang, Yan Peng

“…F-box proteins are essential components of the E3 ubiquitin ligases which are involved in the regulation of almost all life activities such as cell cycle, proliferation, and apoptosis, which have become an important research and drug target. …”
Get full text

Fragrant olive (Osmanthus fragrans Lour.) flower extract attenuates dexamethasone-induced muscle atrophy through stimulation of PI3K/Akt pathway in C2C12 myotubes and C57BL/6 mice by Taeuk Kim, Seungok Lee, Sein Lee, Hyejung Han, Chul-Hong Kim, Dong-Woo Lee, Jae-Kwan Hwang

“…Moreover, OFWE treatment reduced muscle protein degradation by regulating the nuclear translocation of forkhead box O3a and the expression of E3 ubiquitin ligases. In an animal model, OFWE administration was shown to increase muscle mass, myofiber size, and exercise capacity. …”
Get full text

Global Transcriptomic Analysis of Inbred Lines Reveal Candidate Genes for Response to Maize Lethal Necrosis by Ann Murithi, Gayathri Panangipalli, Zhengyu Wen, Michael S. Olsen, Thomas Lübberstedt, Kanwarpal S. Dhugga, Mark Jung

“…Key findings included the identification of components of the plant innate immune system, such as differentially regulated R genes (mainly LRRs), and activation/deactivation of virus resistance pathways, including RNA interference (RNAi) via <i>Argonaute</i> (AGO), <i>Dicer-like proteins</i>, and the ubiquitin–proteasome system (UPS) via <i>RING/U-box</i> and <i>ubiquitin ligases</i>. Genes associated with redox signaling, <i>WRKY</i> transcription factors, and cell modification were also differentially expressed. …”
Get full text

Drosophila Cul3 contributes to Diap2-mediated innate immune signaling for antimicrobial defense by Fanrui Kong, Zixuan Wang, Chuchu Zhang, Yihua Xiao, Muhammad Abdul Rehman Saeed, Weini Li, Akira Goto, Qingshuang Cai, Shanming Ji

“…Herein, we investigate the functional role of Cullin-3 (Cul3), one critical constituent of Cullin-RING ubiquitin ligases, in the Drosophila melanogaster (fruit fly) antimicrobial immune defense. …”
Get full text

Identification of potential substrates of LNX1 in chicken cells by Yuhong Liu, Qianmei Gao, Qi Zhang, Chen Li, Sha Liu, Meng Su, Danli Song, Guiping Zhao, Qinghe Li

“…LNX1, an E3 ubiquitin ligase, catalyzes the ubiquitination and subsequent degradation of specific substrate proteins. …”
Get full text

LUBAC Formation Is Impaired in the Livers of Mice with MCD-Dependent Nonalcoholic Steatohepatitis by Yasuka Matsunaga, Yusuke Nakatsu, Toshiaki Fukushima, Hirofumi Okubo, Misaki Iwashita, Hideyuki Sakoda, Midori Fujishiro, Takeshi Yamamotoya, Akifumi Kushiyama, Shin-ichiro Takahashi, Yoshihiro Tsuchiya, Hideaki Kamata, Fuminori Tokunaga, Kazuhiro Iwai, Tomoichiro Asano

“…Recently, it was reported that the new ubiquitin ligase complex termed linear ubiquitin chain assembly complex (LUBAC), composed of SHARPIN (SHANK-associated RH domain-interacting protein), HOIL-1L (longer isoform of heme-oxidized iron-regulatory protein 2 ubiquitin ligase-1), and HOIP (HOIL-1L interacting protein), forms linear ubiquitin on NF-κB essential modulator (NEMO) and thereby induces NF-κB pathway activation. …”
Get full text

SCRAPPER Regulates the Thresholds of Long-Term Potentiation/Depression, the Bidirectional Synaptic Plasticity in Hippocampal CA3-CA1 Synapses by Hiroshi Takagi, Mitsutoshi Setou, Seiji Ito, Ikuko Yao

“…Here, we recorded the induction of long-term potentiation/depression (LTP/LTD) in CA3-CA1 synapses in E3 ubiquitin ligase SCRAPPER-deficient hippocampal slices. …”
Get full text

F-box protein Fbx23 acts as a transcriptional coactivator to recognize and activate transcription factor Ace1. by Zhongjiao Liu, Kexuan Ma, Panpan Zhang, Siqi Zhang, Xin Song, Yuqi Qin

“…The limited number of identified ubiquitin ligase-substrate pairs is a major bottleneck in the ubiquitination field. …”
Get full text

Different Angiogenic Potential in Low and High Grade Sporadic Clear Cell Renal Cell Carcinoma Is Not Related to Alterations in the von Hippel–Lindau Gene by Marcella M. Baldewijns, Iris J. H. van Vlodrop, Kim M. Smits, Peter B. Vermeulen, Gert G. Van den Eynden, Fiona Schot, Tania Roskams, Hein van Poppel, Manon van Engeland, Adriaan P. de Bruïne

“…Background: von Hippel–Lindau (VHL) inactivation is common in sporadic clear cell renal cell carcinomas (ccRCC). pVHL is part of the ubiquitin ligase complex that targets the alpha subunits of hypoxia-inducible transcription factor (HIF) for degradation under well-oxygenated conditions. …”
Get full text

Disturbed shear stress promotes atherosclerosis through TRIM21‐regulated MAPK6 degradation and consequent endothelial inflammation by Feng Wang, Shu‐Yu Wang, Yue Gu, Shuai Luo, Ai‐Qun Chen, Chao‐Hua Kong, Wen‐Ying Zhou, Li‐Guo Wang, Zhi‐Mei Wang, Guang‐Feng Zuo, Xiao‐Fei Gao, Jun‐Jie Zhang, Shao‐Liang Chen

“…Key points Disturbed flow activates the ubiquitin‒proteasome degradation pathway of MAPK6 in endothelial cells, which is contingent on the binding of the ubiquitin ligase TRIM21 to MAPK6. Endothelial MAPK6 has an advantageous impact on decelerating plaque progression. …”
Get full text

Understanding the Pathogenesis of Angelman Syndrome through Animal Models by Nihar Ranjan Jana

“…The UBE3A gene encodes a 100 kDa protein that functions as ubiquitin ligase and transcriptional coactivator. Emerging evidence now indicates that UBE3A plays a very important role in synaptic function and in regulation of activity-dependent synaptic plasticity. …”
Get full text

Identification of novel 7-hydroxycoumarin derivatives as ELOC binders with potential to modulate CRL2 complex formation by Yonghyeok Kim, Seon Jeong Baek, Eun-Kyung Yoon, Minhee Choi, Jung-Hoon Kim, Kyungtae Kim, Chi Hoon Park, Byung Il Lee

“…Abstract The VHL-containing cullin-RING E3 ubiquitin ligase (CRL2VHL) complex is an E3 ligase commonly used in targeted protein degradation (TPD). …”
Get full text

Targeting MDM2 affects spastin protein levels and functions: implications for HSP treatment by Francesca Sardina, Federica Polverino, Sonia Valentini, Claudia Carsetti, Elisabetta Falvo, Giada Tisci, Silvia Soddu, Fabiola Moretti, Alessandro Paiardini, Cinzia Rinaldo

“…By biochemical and functional experiments, we demonstrate that MDM2 binds spastin and regulates its levels in a post-transcriptional manner independently of the E3 ubiquitin ligase activity. Of relevance, treatment of spastin-deficient cells with the MDM2 inhibitor Nutlin-3a can restore spastin levels and functions, such as cytokinetic abscission and sorting of transferrin receptor. …”
Get full text

Potential application of proteolysis targeting chimera (PROTAC) modification technology in natural products for their targeted protein degradation by Guliang Yang, Haiyan Zhong, Xinxin Xia, Zhiwen Qi, Chengzhang Wang, Shiming Li

“…As the agents in protein degradation dependent on ubiquitin ligase, the bifunctional molecule connects the target protein ligand and E3 ligase ligand together via an appropriate linker. …”
Get full text

Identification of MORF4L1 as an endogenous substrate of CRBN and its potential role as a therapeutic target in cancer by Luyao Zhang, Shunfang Liu, Jingliang He, Zhongke Hu, Lan Zhu, Hongyi Huang, Qi Gao, Dan Wang, Lu Chen, Xingyu Zhang, Ruotong Liu, Jiayun Wang, Yizhuo Song, Kaile Zeng, Xiuming Li, Yulu Chen, Xun Zou, Shaojie Ma, Xiujun Wang, Guofeng Xu, Wei Liu, Bin Liu

“…The cereblon (CRBN) E3 ubiquitin ligase complex is a crucial component of the UPS, particularly in modulating protein degradation in response to small-molecule modulators like thalidomide. …”
Get full text

Genetically-encoded targeted protein degradation technology to remove endogenous condensation-prone proteins and improve crop performance by Ming Luo, Sitao Zhu, Hua Dang, Qing Wen, Ruixia Niu, Jiawei Long, Zhao Wang, Yongjia Tong, Yuese Ning, Meng Yuan, Guoyong Xu

“…Here, we identify the E3 ubiquitin ligase E3TCD1 and develope a Targeted Condensation-prone-protein Degradation (TCD) strategy. …”
Get full text

Transposon mediated functional genomic screening for BRAF inhibitor resistance reveals convergent Hippo and MAPK pathway activation events by Li Chen, Iulian Pruteanu-Malinici, Anahita Dastur, Xunqin Yin, Dennie Frederick, Ruslan I. Sadreyev, Cyril H. Benes

“…Moreover, we illustrated the pivotal role of the Hippo pathway effector TAZ (encoded by the WWTR1 gene) in mediating BRAF inhibition resistance through transcriptional regulation of receptor tyrosine kinases and through interactions with the E3 ubiquitin ligase NEDD4L.…”
Get full text

Activation of lysophagy by a TBK1-SCFFBXO3-TMEM192-TAX1BP1 axis in response to lysosomal damage by Na Yeon Park, Doo Sin Jo, Jae-Yoon Yang, Ji-Eun Bae, Joon Bum Kim, Yong Hwan Kim, Seong Hyun Kim, Pansoo Kim, Dong-Seok Lee, Tamotsu Yoshimori, Eun-Kyeong Jo, Eunbyul Yeom, Dong-Hyung Cho

“…We screen a ubiquitination-related compound library and determine that the substrate recognition component of the SCF-type E3 ubiquitin ligase complex, SCFFBXO3(FBXO3), which is a critical lysophagy regulator. …”
Get full text