The histone demethylase KDM5C enhances the sensitivity of acute myeloid leukemia cells to lenalidomide by stabilizing cereblon by Lu Zou, Dan Cao, Qing Sun, Wenjun Yu, Bingzong Li, Guoqiang Xu, Liang Zhou

“…Len binds to CRBN, recruits IKZF1/IKZF3, and promotes their ubiquitination and degradation, through which Len exhibits its antileukemia and antimyeloma activity. …”
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Structural insights into the LGR4-RSPO2-ZNRF3 complexes regulating WNT/β-catenin signaling by Lu Wang, Fangzheng Hu, Qianqian Cui, Huarui Qiao, Lingyun Li, Tengjie Geng, Yuying Li, Zengchao Sun, Siyu Zhou, Zhongyun Lan, Shaojue Guo, Ying Hu, Jiqiu Wang, Qilun Yang, Zenan Wang, Yuanyuan Dai, Yong Geng

“…ZNRF3/RNF43 modulates Frizzleds through ubiquitination, dampening WNT/β-catenin signaling. Conversely, RSPO1-4 binding to LGR4-6 and ZNRF3/RNF43 enhances WNT/β-catenin signaling3–5. …”
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UBE2T/CDC42/CD276 signaling axis mediates brain metastasis of triple-negative breast cancer via lysosomal autophagy by Lin Li, Rong Fu, Yan Chen, Jin Yao, Xiaobing Jiang, Tao Liang, Jun jun Li, Qian zhi Chen, Liang Liang Shi, Ming Xing Xie, Xin Wei Qiao, Qi Hong Cheng, Min Jie Wang

“…Finally, animal experimental results also showed that inhibition of UBE2T elevated the TNBC sensitivity to immune checkpoint CD276 blockade and inhibited BrM of TNBC.Conclusions In conclusion, our results indicate a new mechanism whereby UBE2T-mediated ubiquitination positively controls the UBE2T/CDC42/CD276 axis to upregulate tumor cell expression of CD276 and thereby impair CD8+ T cells function, ultimately leading to tumor cell immune escape and BrM.…”
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GC-derived exosomal circMAN1A2 promotes cancer progression and suppresses T-cell antitumour immunity by inhibiting FBXW11-mediated SFPQ degradation by Yikai Shen, Jie Lin, Tianlu Jiang, Xusheng Shen, Ying Li, Yiwang Fu, Penghui Xu, Lang Fang, Zetian Chen, Hongxin Huang, Yiwen Xia, Zekuan Xu, Linjun Wang

“…Mechanistically, circMAN1A2 competed with FBXW11 for binding to SFPQ, preventing FBXW11-mediated k48-linked ubiquitination and SFPQ protein degradation, thereby stabilizing SFPQ expression. …”
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Epigenetics disruptions enabled by porphyrin-derived metal-organic frameworks disarm resistances to sonocatalytic ROS anti-tumor actions by Yan Zhang, Dou Du, Chao Fang, Xin Yu, Yujia Fang, Xinyu Liu, Di Ou, Haohao Yin, Hui Liu, Taixia Wang, Lu Lu, Xiaolong Li, Kun Zhang

“…Herein, we proposed an epigenetic deubiquitination disruption strategy to disarm the ubiquitination-deubiquitination balance-induced resistances to ROS production and ROS-based anti-tumor action for potentiating sonodynamic treatment (SDT) efficiency. …”
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A structure-based designed small molecule depletes hRpn13Pru and a select group of KEN box proteins by Xiuxiu Lu, Monika Chandravanshi, Venkata R. Sabbasani, Snehal Gaikwad, V. Keith Hughitt, Nana Gyabaah-Kessie, Bradley T. Scroggins, Sudipto Das, Wazo Myint, Michelle E. Clapp, Charles D. Schwieters, Marzena A. Dyba, Derek L. Bolhuis, Janusz W. Koscielniak, Thorkell Andresson, Michael J. Emanuele, Nicholas G. Brown, Hiroshi Matsuo, Raj Chari, Deborah E. Citrin, Beverly A. Mock, Rolf E. Swenson, Kylie J. Walters

“…Here, we show that XL44 induces ubiquitin-dependent loss of hRpn13Pru and ubiquitin-independent loss of select KEN box containing proteins.…”
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Frk positively regulates innate antiviral immunity by phosphorylating TBK1 by Xiaomei Zhang, Ying You, Tingrong Xiong, Tingrong Xiong, Xiaokai Zhang, Haibo Wang, Jinxia Geng, Miao Wang, Yanyan Xu, Shanshan Gao, Shanshan Gao, Xiaoyan Wu, Yue Zheng, Xianhua Wen, Haoyu Yang, Yu Wang, Yu Wang, Xiaohua Wen, Congcong Zhao

“…Mechanistically, Frk promotes the K63 ubiquitination of TBK1 and subsequent activation of the transcription factor IRF3 by phosphorylating TBK1 at tyrosine residues 174 and 179, thereby enhancing the production of IFN-β in macrophages. …”
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Synaptotagmin-1 attenuates myocardial programmed necrosis and ischemia/reperfusion injury through the mitochondrial pathway by Teng Sun, Jialei Li, Shuang Wang, Yu Han, Xiangyu Tao, Min Yuan, Zhijie Jing, Ting Liu, Yuehong Qi, Siqi Liu, Yanlin Feng, Jiasong Chang, Lan Zhou, Lijuan Gao, Jianyun Shi, Ruihong Ning, Jimin Cao

“…In exploring the underlying mechanisms, we found that Syt1 interacted with Parkin and promoted Parkin-catalyzed CypD ubiquitination, thus inhibited mitochondrial membrane permeability transition pore (mPTP) opening and ultimately suppressed cardiomyocyte necrosis. …”
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MELK prevents radiofrequency ablation-induced immunogenic cell death and antitumor immune response by stabilizing FABP5 in hepatocellular malignancies by Bu-Fu Tang, Wang-Ting Xu, Shi-Ji Fang, Jin-Yu Zhu, Rong-Fang Qiu, Lin Shen, Yang Yang, Qiao-You Weng, Ya-Jie Wang, Jia-Yi Ding, Xiao-Jie Zhang, Wei-Qian Chen, Li-Yun Zheng, Jing-Jing Song, Biao Chen, Zhong-Wei Zhao, Min-Jiang Chen, Jian-Song Ji

“…Mechanically, MELK binds to fatty acid-binding protein 5 (FABP5), and affects its ubiquitination through the K48R pathway to increase its stability, thereby activating protein kinase B (Akt)/mammalian target of rapamycin (mTOR) signaling axis to weaken the RFA-mediated antitumor effect. …”
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Disruption of tumor-intrinsic PGAM5 increases anti-PD-1 efficacy through the CCL2 signaling pathway by Yan Li, Hong Wang, Xiaoyang Li, Yuan He, Huiquan Liu, Dong Han, Ting Mei, Yixuan Li, Zilong Xu, Xiaoying Wei, Jianguo Wang, Peijie Zhou, Yuwen Wang, Ziye Li, Junhao Ning, Anlin Wang, Jingjing Cheng, Dong Qian

“…Mechanistically, in HCC cells PGAM5 deficiency inhibited mitochondria fission by promoting TRIM28 binding with DRP1, which increased ubiquitination and degradation of DRP1. Tumor-intrinsic PGAM5 deficiency mediated mitochondria fusion and reduced cytosolic mtDNA stress which attenuated TLR9 activation and downstream NF-κB-regulated CCL2 secretion. …”
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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. …”
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Chemical tools to define and manipulate interferon-inducible Ubl protease USP18 by Griffin J. Davis, Anthony O. Omole, Yejin Jung, Wioletta Rut, Ronald Holewinski, Kiall F. Suazo, Hong-Rae Kim, Mo Yang, Thorkell Andresson, Marcin Drag, Euna Yoo

“…Abstract Ubiquitin-specific protease 18 (USP18) is a multifunctional cysteine protease primarily responsible for deconjugating the interferon-inducible ubiquitin-like modifier ISG15 from protein substrates. …”
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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

“…It is highly selective and efficient to induce the ubiquitin-mediated degradation of targeted binding proteins. …”
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MAP1B Interaction with the FW Domain of the Autophagic Receptor Nbr1 Facilitates Its Association to the Microtubule Network by Katie Marchbank, Sarah Waters, Roland G. Roberts, Ellen Solomon, Caroline A. Whitehouse

“…This is the first evidence that links the ubiquitin receptor Nbr1, which shuttles ubiquitinated proteins to be degraded by autophagy, to the microtubule network.…”
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Protein Ubiquitylation in Pancreatic Cancer by Thomas Bonacci, Julie Roignot, Philippe Soubeyran

“…Taking into account that ubiquitylation machinery is a three-step process involving hundreds of proteins, which is countered by numerous ubiquitin hydrolases, and that the function of ubiquitylation relies on the recognition of the ubiquitin signals by hundreds of proteins containing a ubiquitin binding domain (including the proteasome), the number of possible therapeutic targets is exceptionally vast and will need to be explored carefully for each disease. …”
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A novel UBA1 gene mutation in a patient with infantile respiratory distress syndrome by Masafumi Miyata, Arisa Kojima, Yuri Kawai, Hidetoshi Uchida, Hiroko Boda, Naoko Ishihara, Hidehito Inagaki, Tetsushi Yoshikawa, Hiroki Kurahashi

“…Abstract UBA1 is an E1 ubiquitin-activating enzyme that initiates the ubiquitylation of target proteins and is thus a key component of the ubiquitin signaling pathway. …”
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Proteomic analysis to explore potential mechanism underlying pseudomale sperm defect in Cynoglossus semilaevis by Xihong Li, Lu Li, Zhongkai Cui, Ming Li, Xuexue Sun, Zhijie Li, Zhangfan Chen, Lanqing Ding, Dongdong Xu, Wenteng Xu

“…Interestingly, ten molecular chaperones including four heat shock proteins (Hsp90aa1.2, Hsp90ab1, Hsp90b1, and Hsc71/Hspa8) and six chaperonin containing T-complex protein 1 (TCP1) subunits (Cct1, Cct2, Cct3, Cct4, Cct5, and Cct7) were identified, and they were up-regulated in pseudomale. Ubiquitin-related proteins including ubiquitin like 4 A (Ubl4a) and NEDD8 ubiquitin like modifier (NEDD8), proteasome subunits such as proteasome 26S subunit, non-ATPase 14 (Psmd14) and proteasome 26S subunit, ATPase 6 (Psmc6), and redox-related proteins like thioredoxin-disulfide reductase (Txnrd3) and thioredoxin (Trx1) were also found in PPI network. …”
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Deubiquitinases: Novel Therapeutic Targets in Immune Surveillance? by Gloria Lopez-Castejon, Mariola J. Edelmann

“…Accumulative evidence shows that the ubiquitin system, and in particular ubiquitin-specific isopeptidases also known as deubiquitinases (DUBs), plays crucial roles in the control of these immune pathways. …”
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A root system architecture regulator modulates OsPIN2 polar localization in rice by Yong Li, Meiyan Ren, Yunrong Wu, Lingling Wang, Keju Zhao, Hongsheng Gao, Mengzhen Li, Yu Liu, Jianshu Zhu, Jiming Xu, Xiaorong Mo, Zhongchang Wu, Chungui Lu, Shaojian Zheng, Chuanzao Mao

“…OsGLS1 encodes a RING finger E3 ubiquitin ligase mainly localizing at the basal plasma membrane (PM) in several root cell types when phosphorylated on its Ser-30 residue. …”
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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. …”
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