Article
Cell Biology
Sirisha Mukkavalli, Jacob Aaron Klickstein, Betty Ortiz, Peter Juo, Malavika Raman
Summary: This study identifies the important role of p97-UBXN1 in the clearance of protein aggregates, demonstrating that UBXN1 knockout affects the formation of aggresomes, while mutations in p97 result in multi-system proteinopathies.
JOURNAL OF CELL SCIENCE
(2021)
Article
Biochemistry & Molecular Biology
Chenliang Zhang, Qiulin Tang, Hongwei Xia, Huanji Xu, Feng Bi
Summary: Protein aggregation and degradation via autophagy (aggrephagy) are important cellular mechanisms to remove misfolded polypeptides when proteasome function is impaired. A protein complex consisting of heat shock protein 70 (Hsp70), cochaperone CHIP, and co-chaperone BAG3 has been shown to be involved in activating protein aggregation. However, the specific mechanisms of how this complex functions in protein degradation are not yet well understood. This study reveals that the M2 isoform of pyruvate kinase (PKM2) promotes the aggregation of ubiquitinated proteins under proteasome stress. Knockout or knockdown of PKM2 worsens the sensitivity of cells to proteasome inhibitors. Additionally, PKM2 facilitates the interaction between BAG3, CHIP, and HSP70 upon proteasome inhibition. These findings suggest that PKM2 plays a regulatory role in the formation of the CHIP-HSP70-BAG3 complex and promotes the aggregation of ubiquitinated misfolded proteins in response to proteasome stress.
Article
Biochemistry & Molecular Biology
Vu Thuy Khanh Le-Trilling, Sofia Banchenko, Darius Paydar, Pia Madeleine Leipe, Lukas Binting, Simon Lauer, Andrea Graziadei, Robin Klingen, Christine Gotthold, Joerg Buerger, Thilo Bracht, Barbara Sitek, Robert Jan Lebbink, Anna Malyshkina, Thorsten Mielke, Juri Rappsilber, Christian M. T. Spahn, Sebastian Voigt, Mirko Trilling, David Schwefel
Summary: This study revealed that rat cytomegalovirus infection induces the loss of transcription factor STAT2, which is crucial for antiviral interferon signaling. It was found that viral protein E27 exploits the host-cell CRL4 complexes to degrade STAT2 through poly-ubiquitylation. Furthermore, structural analyses showed that E27 recruits STAT2 through a bipartite binding interface, partially overlapping with the IRF9 binding site.
Article
Biochemistry & Molecular Biology
Chenliang Zhang, YiChun Duan, Chen Huang, Liping Li
Summary: This study explores the role of SQSTM1 phosphorylation in the formation of aggresomes under proteasome inhibition. It finds that inhibiting SQSTM1 S403 phosphorylation promotes the formation of aggresomes for ubiquitinated proteins, while phosphorylation of SQSTM1 T269/S272 inhibits S403 phosphorylation and enhances aggresome formation, protecting cells from proteotoxicity.
CELLULAR & MOLECULAR BIOLOGY LETTERS
(2023)
Article
Environmental Sciences
Xinming Shen, Wenxin Hu, Chenke Xu, Cheng Xu, Yi Wan, Jianying Hu
Summary: The study found that benzotriazole ultraviolet stabilizers (BUVSs) commonly detected in the environment can promote foam cell formation in macrophages, thereby increasing the risk of atherosclerosis in humans.
ENVIRONMENTAL POLLUTION
(2023)
Article
Virology
Xue-Hui Ma, Yong-Xuan Yao, Xian-Zhang Wang, Yue-Peng Zhou, Sheng-Nan Huang, Dong Li, Meng-Jie Mei, Jing-Peng Wu, Yu-Ting Pan, Shuang Cheng, Xuan Jiang, Jin-Yan Sun, Wen-Bo Zeng, Sitang Gong, Han Cheng, Min-Hua Luo, Bo Yang
Summary: During the coevolution of human cytomegalovirus (HCMV) and humans, the host has developed a defense system while the virus has devised strategies to evade detection. MORC3, a component of PML-NBs, is identified as a restriction factor targeting HCMV infection. HCMV induces temporary reduction of MORC3 protein level to evade its repression against immediate-early gene expression.
JOURNAL OF MEDICAL VIROLOGY
(2022)
Review
Cell Biology
Jason Q. Tang, Mary M. Marchand, Gianluca Veggiani
Summary: Protein turnover, regulated by the ubiquitin-proteasome system (UPS), is important for cellular homeostasis. Dysregulation of the UPS is associated with diseases and UPS enzymes are attractive therapeutic targets. However, redundancies of UPS enzymes make it challenging to identify precise drug targets. Engineered ubiquitin has emerged as a promising alternative to guide the development of small molecules targeting novel surfaces.
Article
Biochemistry & Molecular Biology
Zhefan Stephen Chen, Mingqi Yan, Wenhui Pei, Bowen Yan, Caoxing Huang, Ho Yin Edwin Chan
Summary: In this study, the potential therapeutic effect of lignin-carbohydrate complexes (LCCs) on polyglutamine diseases was investigated. LCCs isolated from bamboo and poplar were found to effectively eliminate protein aggregation and rescue photoreceptor degeneration. Mechanistically, LCCs were shown to upregulate proteasomal activity, which was crucial for their beneficial effects on polyglutamine neurotoxicity.
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
(2022)
Article
Medicine, Research & Experimental
Weiyi Zhang, Qian Che, Hongsheng Tan, Xin Qi, Dehai Li, Tianjiao Zhu, Ming Liu
Summary: Researchers isolated a novel antimycin alkaloid called antimycin A2c (AE) from a marine-derived Streptomyces sp. THS-55 and determined its chemical structure through extensive spectra. They also investigated the specific mechanism of AE in HPV-infected cervical cancer.
Article
Oncology
Jianli Ma, Junwen Zhu, Jingtong Li, Ji Liu, Xiaofeng Kang, Jinming Yu
Summary: Radiotherapy has demonstrated efficacy in breast cancer, but resistance remains a challenge. Mitochondria, as a crucial regulator of redox homeostasis, have emerged as a target for radiotherapy. This study identified ENO1 as a prognostic marker for radiotherapy efficacy in breast cancer. ENO1 reduces reactive oxygen species and apoptosis through modulation of mitochondrial homeostasis, leading to radiotherapeutic resistance. LINC00663 was identified as an upstream regulator of ENO1, and its downregulation enhances radiotherapeutic sensitivity in breast cancer by regulating ENO1 protein stability.
Article
Oncology
Muhammad Shahzad Ali, Cristina Panuzzo, Chiara Calabrese, Alessandro Maglione, Rocco Piazza, Daniela Cilloni, Giuseppe Saglio, Barbara Pergolizzi, Enrico Bracco
Summary: This study provides original evidence on the potential tumor-suppressing or -promoting properties of HERC1 in myeloid related blood disorders. The HERC1 gene expression is regulated in various myeloid related disorders, suggesting roles in disease progression. The physical interaction between HERC1 and BCR-ABL1 kinase activity indicates a potential mechanism underlying the pathogenesis of these disorders.
Article
Cell Biology
Yusuke Nishimura, Jitpisute Chunthorng-Orn, Samuel Lord, Ibrahim Musa, Peter Dawson, Lars Holm, Yu-Chiang Lai
Summary: In this study, the researchers showed that Atrogin-1 and MuRF1 protein contents are regulated by different mechanisms, specifically the downstream of Akt, and that Atrogin-1 protein content can be regulated by the rapamycin-sensitive mTOR-S6K1-dependent signaling pathway.
AMERICAN JOURNAL OF PHYSIOLOGY-CELL PHYSIOLOGY
(2022)
Article
Virology
Linchao Wang, Yanhong Song, Xiaolong Yan, Tianjun Xu
Summary: This study identifies a circRNA called circVPS13D as a negative regulator in the antiviral immune responses of fish. It encodes a protein called VPS13D-170aa which targets MAVS and inhibits the RLRs antiviral signaling pathway, leading to the suppression of type I interferon production.
JOURNAL OF VIROLOGY
(2023)
Article
Endocrinology & Metabolism
Nienke Willemsen, Isabel Arigoni, Maja Studencka-Turski, Elke Krueger, Alexander Bartell
Summary: Regulation of proteasomal activity is crucial for cellular proteostasis and function. This study investigates the role of proteasome subunits Psmb4 and Psmb8 in brown adipocyte differentiation, function, and proteostasis. The findings suggest that Psmb4 is required for adipocyte development and function, and its loss disrupts proteostasis and impairs adipogenesis. Atf3 is identified as a key effector of inflammation and blocking adipogenesis. Additionally, the study highlights the involvement of Nfe2l1 in maintaining proteostasis under these conditions.
MOLECULAR METABOLISM
(2022)
Article
Microbiology
Bingmei Dong, Feng Li, Jinliang Wang, Sufang Lv, Lizhong Miao, Guangjun Guo, Zhiqiang Shen
Summary: This study investigated the roles of ubiquitin-proteasome system (UPS) and autophagy-lysosome pathway (ALP) in Brucella.suis (B.suis) infection in murine macrophages. The results showed that B.suis activated ALP and UPS, and both pathways contributed to the intracellular proliferation of B.suis. Furthermore, the study demonstrated that ALP was activated following UPS inhibition, and UPS had a stronger ability than ALP in promoting intracellular proliferation of B.suis.
VETERINARY MICROBIOLOGY
(2023)
Article
Cell Biology
Po-Yuan Hsu, Edward Hsi, Tzu-Ming Wang, Ruey-Tay Lin, Yi-Chu Liao, Suh-Hang H. Juo
JOURNAL OF CELLULAR AND MOLECULAR MEDICINE
(2017)
Article
Oncology
Li-Ting Wang, Shyh-Shin Chiou, Chee-Yin Chai, Edward Hsi, Shen-Nien Wang, Shau-Ku Huang, Shih-Hsien Hsu
Article
Medicine, General & Internal
Hsiu-Fen Lin, Edward Hsi, Ling-Chun Huang, Yi-Chu Liao, Suh-Hang H. Juo, Ruey-Tay Lin
JOURNAL OF INVESTIGATIVE MEDICINE
(2017)
Article
Chemistry, Medicinal
Yu-Sheng Lee, Tsai-Hui Duh, Shu-Sheng Siao, Rey-Chang Chang, Shang-Kwei Wang, Chang-Yih Duh
Article
Biochemistry & Molecular Biology
Shih-Hsien Hsu, Li-Ting Wang, Chee-Yin Chai, Chi-Cheng Wu, Edward Hsi, Shyh-Shin Chiou, Shen-Nien Wang
MOLECULAR CARCINOGENESIS
(2017)
Article
Oncology
Yung-Song Wang, Edward Hsi, Hsin-Yun Cheng, Shih-Hsien Hsu, Yi-Chu Liao, Suh-Hang H. Juo
Article
Chemistry, Medicinal
Fu-Yun Hsu, Shang-Kwei Wang, Chang-Yih Duh
Article
Chemistry, Medicinal
Xue-Hua Ling, Shang-Kwei Wang, Yun-Hsuan Huang, Min-Jay Huang, Chang-Yih Duh
Article
Ophthalmology
Edward Hsi, Yung-Song Wang, Chia-Wei Huang, Ming-Lung Yu, Suh-Hang Hank Juo, Chung-Ling Liang
INTERNATIONAL JOURNAL OF OPHTHALMOLOGY
(2019)
Article
Environmental Sciences
Chon-Kit Chou, Hurng-Wern Huang, Chun-Feng Yang, Hans-Uwe Dahms, Shih-Shin Liang, Tsu-Nai Wang, Po-Lin Kuo, Edward Hsi, Eing-Mei Tsai, Chien-Chih Chiu
ENVIRONMENTAL TOXICOLOGY
(2019)
Article
Chemistry, Medicinal
Che-Yen Chiu, Xue-Hua Ling, Shang-Kwei Wang, Chang-Yih Duh
Article
Otorhinolaryngology
Chen-Yu Chien, Shu-Yu Tai, Kuan-Hui Li, Hua-Ling Yang, Leong-Perng Chan, Edward Hsi, Ling-Feng Wang, Kuen-Yao Ho, Ning-Chia Chang
Summary: The study analyzed the association of IL-1R gene SNPs with SSNHL in Taiwan, finding significant associations with SNPs rs2234650 and rs4141134. The findings suggest that IL1R1 and IL1R2 gene polymorphisms may contribute to an increased risk of SSNHL in Taiwan.
JOURNAL OF OTOLARYNGOLOGY-HEAD & NECK SURGERY
(2021)
Meeting Abstract
Oncology
Kwei-Yan Liu, Li-Ting Wang, Shyh-Shin Chiou, Chee-Yin Chai, Edward Hsi, Shen-Nien Wang, Shau-Ku Huang, Shih-Hsien Hsu
Article
Oncology
Li-Ting Wang, Shyh-Shin Chiou, Chee-Yin Chai, Edward Hsi, Kazunari K. Yokoyama, Shen-Nien Wang, Shau-Ku Huang, Shih-Hsien Hsu
Correction
Ophthalmology
Edward Hsi, Ku-Chung Chen, Wan-Shu Chang, Ming-Lung Yu, Chung-Ling Liang, Suh-Hang Hank
INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE
(2017)