Review
Cell Biology
Alexandra Daks, Olga Fedorova, Sergey Parfenyev, Ivan Nevzorov, Oleg Shuvalov, Nickolai A. Barlev
Summary: The p53-dependent ubiquitin ligase Pirh2 regulates proteins involved in cancer-associated processes. This review summarizes the regulation, protein targets, and role of Pirh2 in various diseases, making it a promising therapeutic target.
Article
Multidisciplinary Sciences
Melissa S. Traver, Bonnie Bartel
Summary: Lipid droplets are conserved organelles that regulate energy homeostasis by storing and releasing neutral lipids. This study identified MIEL1 as a protein that modulates lipid droplet dynamics by ubiquitinating and degrading the seed lipid droplet protein OLE1. The human homolog of MIEL1, PIRH2, was also found to be involved in lipid catabolism and peroxisome biology in mammals.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2023)
Review
Immunology
Maoyu Wang, Zhensheng Zhang, Zhizhou Li, Yasheng Zhu, Chuanliang Xu
Summary: With the increasing incidence of bladder cancer, there has been a focus on understanding its mechanism and developing new treatment strategies. The introduction of immune checkpoint inhibitor-based immunotherapy has shown great promise in treating advanced bladder cancer and improving patients' survival. The ubiquitin-proteasome system, which plays a crucial role in various biological processes, has been found to be involved in bladder cancer. This review summarizes the recent progress in understanding the role of E3 ubiquitin ligases and deubiquitinases in bladder cancer tumorigenesis and highlights their implications for bladder cancer immunotherapies.
FRONTIERS IN IMMUNOLOGY
(2023)
Review
Biochemistry & Molecular Biology
Yu Meng, Huiyan Sun, Yayun Li, Shuang Zhao, Juan Su, Furong Zeng, Guangtong Deng, Xiang Chen
Summary: Ferroptosis is regulated by ubiquitination at post-translational level, in which E3 ubiquitin ligases (E3s) and deubiquitinating enzymes (DUBs) play crucial roles. The dysregulation of ubiquitin system enzymes contributes to the progression of multiple cancers. Understanding the regulatory networks of ferroptosis mediated by E3s or DUBs may provide new opportunities for cancer therapy.
INTERNATIONAL JOURNAL OF BIOLOGICAL SCIENCES
(2022)
Review
Oncology
Hang Yang, Huihan Ai, Jialin Zhang, Jie Ma, Kangdong Liu, Zhi Li
Summary: Gastric cancer is a common and deadly disease due to the lack of effective drugs and targets for therapy. The ubiquitin-proteasome system (UPS), consisting of E1, E2, and E3 enzymes and proteasome, plays a significant role in gastric cancer tumorigenesis. Imbalance of UPS disrupts protein homeostasis network during gastric cancer development. Modulating these enzymes and proteasome could be a promising strategy for targeted therapy. Additionally, PROTAC, a novel tool utilizing UPS for protein degradation, is being investigated for cancer drug development. This study aims to analyze abnormal expression enzymes in UPS and identify E3 enzymes suitable for PROTAC development to advance UPS modulator and PROTAC technology for gastric cancer therapy.
FRONTIERS IN ONCOLOGY
(2023)
Article
Multidisciplinary Sciences
Xiaolu Wang, Yao Li, Xiaojie Yan, Qing Yang, Bing Zhang, Ying Zhang, Xinxin Yuan, Chenhao Jiang, Dongxing Chen, Quanyan Liu, Tong Liu, Wenyi Mi, Ying Yu, Cheng Dong
Summary: A study reveals that the E3 ligase Pirh2 degrades aberrant nascent polypeptides by targeting the C-terminal polyalanine degrons. The crystal structure of Pirh2 bound to the polyAla/C-degron is presented, demonstrating the recognition of a C-terminal A/S-X-A-A motif by Pirh2 for substrate degradation.
NATURE COMMUNICATIONS
(2023)
Review
Genetics & Heredity
Kailang Li, Jinyun Li, Meng Ye, Xiaofeng Jin
Summary: Siah2 plays a crucial role in human cancer by promoting tumorigenesis or acting as a tumor suppressor through proteasome-mediated degradation of oncoproteins. It is subject to complex regulation, including phosphorylation by various protein kinases to control stability and activity.
Article
Medicine, General & Internal
Ting-Ting Liu, Heng Yang, Fang-Fang Zhuo, Zhuo Yang, Mei-Mei Zhao, Qiang Guo, Yang Liu, Dan Liu, Ke-Wu Zeng, Peng-Fei Tu
Summary: This study identified a molecular glue named bufalin, which significantly promoted the degradation of E2F2. Unexpectedly, E2F2 was found to undergo ubiquitination and proteasomal degradation via an undisclosed atypical E3 ligase called zinc finger protein 91 (ZFP91). The degradation of E2F2 subsequently led to the transcriptional suppression of multiple oncogenes and inhibited hepatocellular carcinoma growth both in vitro and in vivo.
Article
Pharmacology & Pharmacy
Senfeng Xiang, Xiaoxian Shi, Pengfei Chen, Yifan Chen, Shaowei Bing, Xizhi Jin, Ji Cao, Jinhu Wang, Bo Yang, Xuejing Shao, Qiaojun He, Meidan Ying
Summary: The research focuses on the substrate adaptors of CRL3, specifically the Kelch-like (KLHL) family proteins. The study identified 24 KLHL proteins with tumor promotion function and 13 KLHL proteins with high clinical significance in cancer therapy. Additionally, the novel biological function of KLHL13 as a vital factor contributing to malignant progression in lung cancer was clarified.
PHARMACOLOGICAL RESEARCH
(2021)
Article
Oncology
Engin Demirdizen, Ruslan Al-Ali, Ashwin Narayanan, Xueyuan Sun, Julianna Patricia Varga, Bianca Steffl, Manuela Brom, Damir Krunic, Claudia Schmidt, Gabriele Schmidt, Felix Bestvater, Julian Taranda, Sevin Turcan
Summary: In this study, TRIM67 was found to be upregulated in oligodendrogliomas and induces blebbing-based rounded cell morphology through Rho GTPase/ROCK-mediated signaling. The overexpression of TRIM67 enhances cell motility, reduces cell adherence, accelerates tumor growth, and decreases overall survival rates in patients.
Article
Oncology
Jun Zeng, Xiao-Qing Xiao, Zhi-Yong Zhou
Summary: The SCF E3 ligases have been found to play a promoting role in colorectal cancer by mediating the ubiquitination and degradation of tumor suppressors. In this study, it was discovered that hypoxia activated CUL1 expression in CRC cells. CUL1 formed the SCFFBXL1 complex with RBX1, SKP1, and FBXL1, and this complex specifically ubiquitinated and degraded the MEN1 tumor suppressor. Inhibition of HIF1 alpha or SCFFBXL1 members resulted in the accumulation of MEN1 protein, leading to a significant decrease in cell proliferation and migration in vitro and tumor growth in vivo.
CANCER RESEARCH AND TREATMENT
(2022)
Article
Biochemistry & Molecular Biology
Yubin Xie, Huiqin Li, Xiaotong Luo, Hongyu Li, Qiuyuan Gao, Luowanyue Zhang, Yuyan Teng, Qi Zhao, Zhixiang Zuo, Jian Ren
Summary: The visualization of biological sequences is crucial in the field of molecular and cellular biology. IBS 2.0 is a professional tool that allows concise and clear representation of protein and nucleotide sequences. It provides abundant graphical elements and database visualization module for batch visualization of biological sequences.
NUCLEIC ACIDS RESEARCH
(2022)
Review
Medicine, Research & Experimental
Yongshuo Liu, Honghong Zhou, Xiaolong Tang
Summary: The STUB1 gene encodes the essential E3 ligase CHIP involved in protein quality control. STUB1 is crucial in physiological processes such as aging, autophagy, and bone remodeling. It also plays a tumor-suppressive role by degrading oncoproteins and has recently emerged as a novel player in tumor immunity.
BIOMEDICINE & PHARMACOTHERAPY
(2023)
Review
Pharmacology & Pharmacy
Si-Min Qi, Jinyun Dong, Zhi-Yuan Xu, Xiang-Dong Cheng, Wei-Dong Zhang, Jiang-Jiang Qin
Summary: PROTAC technology is an effective method for degrading target proteins through the ubiquitin-proteasome system, with promising applications in cancer treatment. The first oral PROTACs have shown encouraging results in clinical trials, sparking greater enthusiasm for PROTAC research.
FRONTIERS IN PHARMACOLOGY
(2021)
Review
Oncology
Fengguang Zhai, Jie Wang, Weili Yang, Meng Ye, Xiaofeng Jin
Summary: This paper summarizes the E3 ligases relevant to endometrial carcinoma (EC) and cervical cancer (CC), highlighting their significant roles in the occurrence and progression of these cancers. Additionally, research progress in targeting the ubiquitination process in EC and CC is discussed in this review.
