Article
Biochemistry & Molecular Biology
Xinxing Zhu, Beijia Huang, Fengting Zhao, Jie Lian, Lixiang He, Yangxia Zhang, Longkai Ji, Jinghang Zhang, Xin Yan, Taoling Zeng, Chunya Ma, Yinming Liang, Chen Zhang, Juntang Lin
Summary: NF-kappa B activation leads to MRSA-induced lung inflammation, and FOXN3 can inhibit NF-kappa B signaling to reduce the inflammatory response. FOXN3 competes with I kappa B alpha for binding to hnRNPU, preventing I kappa B alpha degradation and NF-kappa B activation. Phosphorylation of FOXN3 by p38 induces dissociation from hnRNPU, leading to NF-kappa B activation. FOXN3 phosphorylation is clinically correlated with pulmonary inflammatory disorders.
NUCLEIC ACIDS RESEARCH
(2023)
Article
Cell Biology
Tai-Mei Zhang, Li Liao, Shao-Ying Yang, Min-Ying Huang, Yin-Ling Zhang, Ling Deng, Shu-Yuan Hu, Fan Yang, Fang-Lin Zhang, Zhi-Min Shao, Da-Qiang Li
Summary: This study reveals the functional role of TMEM63A in triple-negative breast cancer (TNBC) and provides a new target for TNBC treatment. TMEM63A promotes TNBC cell proliferation, migration, and invasion, as well as tumor growth and lung metastasis in vivo. It interacts with VCP and DERL1 and is regulated by autophagic degradation mediated by TOLLIP. Inhibition of VCP or knockdown of DERL1 attenuates the oncogenic effects of TMEM63A in TNBC progression.
Article
Multidisciplinary Sciences
Yuchen Feng, Aileen R. Ariosa, Ying Yang, Zehan Hu, Joern Dengjel, Daniel J. Klionsky
Summary: Macroautophagy/autophagy is a crucial molecular process for maintaining cellular homeostasis, recycling cytoplasmic materials, and responding to stress conditions. The posttranslational modification of Atg9, including ubiquitination and proteasome-dependent degradation, regulates the level of autophagy in cells.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Article
Virology
Hong Chen, Linshan Jiang, Shu Chen, Qin Hu, Ying Huang, Ying Wu, Weixian Chen
Summary: This study reveals that hepatitis B virus X protein (HBx) inhibits the host antiviral immune response by promoting degradation of cyclic GMP-AMP synthase (cGAS), leading to enhanced replication of hepatitis B virus.
Article
Multidisciplinary Sciences
Zhiqiang Hu, Yingchao Xie, Jiansen Lu, Jianwu Yang, Jiahuan Zhang, Huaji Jiang, Hongyu Li, Yufeng Zhang, Dan Wu, Ke Zeng, Xiaochun Bai, Xiao Yu
Summary: In this study, VANGL2 was found to be an IFN-inducible negative feedback regulator that suppresses IFN-I signaling during VSV infection. VANGL2 interacts with TBK1 and promotes the autophagic degradation of TBK1 via K48-linked polyubiquitination mediated by TRIP. Myeloid-specific deletion of VANGL2 in mice results in enhanced IFN-I production against VSV infection and improved survival. These findings reveal a negative feedback loop of IFN-I signaling through the VANGL2-TRIP-TBK1-OPTN axis and highlight the importance of the crosstalk between IFN-I and autophagy in preventing viral infection. VANGL2 could be a potential clinical therapeutic target for viral infectious diseases, including COVID-19.
Article
Biochemistry & Molecular Biology
Erina Iwabuchi, Yasuhiro Miki, Takashi Suzuki, Hisashi Hirakawa, Takanori Ishida, Hironobu Sasano
Summary: The study investigated the biological functions of hnRNPK in the ER-mediated signaling pathway in breast cancer, finding that hnRNPK interacts with ER alpha and is involved in this pathway. Additionally, hnRNPK expression could potentially be a target for endocrine therapy in ER alpha-positive breast cancer patients.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Oncology
Ying Zhao, Jing Ruan, Zhongding Li, Xian Su, Kangmin Chen, Yimin Lin, Yuepiao Cai, Peng Wang, Baohua Liu, Dirk Schlueter, Guang Liang, Xu Wang
Summary: This study reveals that CCN6 protein levels in breast cancer are regulated by ubiquitination and deubiquitinating enzymes (DUBs). OTUB1 is identified as a novel DUB for CCN6 and inhibits its degradation by interacting with CCN6 and inhibiting its K48 ubiquitination. Deletion of OTUB1 results in decreased CCN6 abundance and increased migration, proliferation, and viability of breast cancer cells, which can be rescued by supplementation of CCN6. Importantly, OTUB1 expression is downregulated in human breast cancer and positively correlated with CCN6 levels.
CLINICAL AND TRANSLATIONAL MEDICINE
(2023)
Article
Cell Biology
Manman Liang, Lijing Wang, Zhengui Sun, Xingwu Chen, Hanli Wang, Lilong Qin, Wenying Zhao, Biao Geng
Summary: This study reveals that TRIM15 is frequently upregulated in NSCLC and associated with poor prognosis. Functionally, TRIM15 promotes proliferation and metastasis of NSCLC cells through its E3 ubiquitin ligase activity. Mechanistically, TRIM15 directly targets Keap1 and promotes its ubiquitination and degradation, resulting in the escape of Nrf2 from Keap1-mediated degradation, subsequently promoting antioxidant response and tumor progression.
CELL COMMUNICATION AND SIGNALING
(2022)
Article
Pharmacology & Pharmacy
HuiTing Liu, ZhiXiang Zhou, HuaNian Deng, Zhen Tian, ZeFan Wu, XiYan Liu, Zhong Ren, ZhiSheng Jiang
Summary: Pathological cardiac hypertrophy is a major cause of heart failure and lacks effective prevention or treatment. This study found that Trim65 inhibits cardiac hypertrophy by suppressing mitochondrial-dependent apoptosis and autophagy pathways. Genes related to mitochondrial-dependent apoptosis and associated with Trim65 could be potential therapeutic targets for cardiac hypertrophy.
EUROPEAN JOURNAL OF PHARMACOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Yiming Tu, Lei Xu, Jia Xu, Zhongyuan Bao, Wei Tian, Yangfan Ye, Guangchi Sun, Zong Miao, Honglu Chao, Yongping You, Ning Liu, Jing Ji
Summary: This study identified USP2 as a new candidate gene that inhibits the development of GBM by deubiquitinating SMAD7 and suppressing the TGF-beta signaling pathway.
Review
Genetics & Heredity
Jiangyan Xu, Jinrong Zhang, Qi-Fen Mao, Jian Wu, Yuan Wang
Summary: This article reviews the recent advances in autophagy and its interaction with the JAK/STAT3 signaling pathway in the pathogenesis, prevention, diagnosis, and treatment of tumors. The JAK/STAT3 pathway plays a key role in regulating cell proliferation, apoptosis, and vascular neogenesis, while autophagy is a fundamental metabolic mechanism for intracellular degradation. Both pathways may have different roles at various stages of tumor development.
FRONTIERS IN GENETICS
(2022)
Article
Immunology
Chunchen Wu, Luzhi Zeng, Wenfu Yi, Yuanjiu Miao, Yihan Liu, Qiming Wang, Shi Liu, Guoping Peng, Zhenhua Zheng, Jianbo Xia
Summary: This study demonstrates that echovirus infection can induce autophagy, which promotes viral replication and VP1 expression in host cells. The mechanism involves the regulation of the mTOR/ULK1 signaling pathway, providing insight into the potential role of autophagy in echovirus infection.
FRONTIERS IN IMMUNOLOGY
(2023)
Article
Chemistry, Medicinal
Xin Han, Lijie Zhao, Weiguo Xiang, Bukeyan Miao, Chong Qin, Mi Wang, Tianfeng Xu, Donna McEachern, Jianfeng Lu, Yu Wang, Hoda Metwally, Chao-Yie Yang, Paul D. D. Kirchhoff, Lu Wang, Aleksas Matvekas, John Takyi-Williams, Bo Wen, Duxin Sun, Mark Ator, Robert Mckean, Shaomeng Wang
Summary: We report the discovery of ARD-2051, a highly potent and orally efficacious androgen receptor (AR) proteolysis-targeting chimera degrader. ARD-2051 demonstrates strong AR protein degradation activity and effectively suppresses AR-regulated genes in prostate cancer cell lines. It shows good oral bioavailability and pharmacokinetic profile in animal models. In addition, ARD-2051 inhibits tumor growth and exhibits no signs of toxicity in mice, making it a promising therapeutic option for AR+ human cancers.
JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Review
Oncology
Seung-Cheol Jee, Heesun Cheong
Summary: Autophagy and mitophagy play important roles in regulating cancer progression. The regulation of autophagy and mitophagy through ubiquitination and deubiquitination of related proteins is crucial for exploiting their potential in cancer development. Understanding the mechanistic association between cancer and autophagy/mitophagy activities regulated by ubiquitin modification of autophagic proteins can lead to potential therapeutic targets for cancer treatment.
Article
Cell Biology
Aifang Cheng, Kai-Hei Tse, Hei-Man Chow, Yunqiao Gan, Xuan Song, Fulin Ma, Yi Xuan Yvonne Qian, Weiyi She, Karl Herrup
Summary: ATM protein is associated with cellular organelles such as synaptic vesicles, endosomes, and lysosomes, with its deficiency impacting autophagy and lysosomal function in neurons. This disruption leads to impaired neuronal functions including synaptic maintenance, neuronal survival, and glucose uptake.