Article
Biochemistry & Molecular Biology
Ayumi Kuga, Kouhei Tsuchida, Harit Panda, Makoto Horiuchi, Akihito Otsuki, Keiko Taguchi, Fumiki Katsuoka, Mikiko Suzuki, Masayuki Yamamoto
Summary: Nrf2 activity is regulated by the Keap1-mediated and beta-TrCP-mediated pathways. When Keap1 activity is suppressed, the beta-TrCP-mediated pathway cooperates with the Keap1-mediated pathway to increase Nrf2 activity, resulting in severe growth retardation and esophageal epithelial abnormalities.
MOLECULAR AND CELLULAR BIOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Mario Vega, Yu Chen, Yijiang Shi, Joseph Gera, Alan Lichtenstein
Summary: DEPTOR is a protein upregulated in multiple myeloma cells, which inhibits mTOR and promotes AKT activation. This study found that the phosphorylation of DEPTOR at serine 235 regulates its stability, and the association of USP-7 with DEPTOR depends on S235 phosphorylation. In addition, the ERK1 pathway maintains AKT activity through phosphorylation of DEPTOR.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2022)
Article
Virology
Wenhui Tu, Jin Liu, Feng Qian, Li Zhu, Ming Li, Hui Zheng, Chuanwu Zhu
Summary: Chronic hepatitis B (CHB) cannot be cured currently, but a functional cure might be possible by reducing hepatitis B surface antigen (HBsAg) levels through protein ubiquitination. Our study confirmed that beta-TrCP is the E3 ubiquitin ligase of HBsAg, and can degrade HBsAg through the proteasome pathway. Furthermore, beta-TrCP affects the K48-linked polyubiquitin chain by acting on Myc-HBsAg. Thus, targeting the ubiquitin degradation pathway of HBsAg may help in achieving a functional cure for CHB.
JOURNAL OF MEDICAL VIROLOGY
(2023)
Article
Cell Biology
Tao Hou, Weichao Dan, Tianjie Liu, Bo Liu, Yi Wei, Chenyang Yue, Taotao Que, Yuzeshi Lei, Zixi Wang, Jin Zeng, Yizeng Fan, Lei Li
Summary: This study reveals that the deubiquitinating enzyme OTUD5 activates the mTOR signaling pathway to promote bladder cancer progression. OTUD5 stabilizes the function of RNF186, a RING-type E3 ligase, leading to the degradation of sestrin2, an inhibitor of the mTOR signaling pathway.
CELL DEATH & DISEASE
(2022)
Article
Cell Biology
Susu Guo, Yuxin Chen, Yueyue Yang, Xiao Zhang, Lifang Ma, Xiangfei Xue, Yongxia Qiao, Jiayi Wang
Summary: This study demonstrates that TRIB2 reduces Ub levels by stimulating proteasome degradation and interacts with PCBP2 to modulate PSMB5 activity, which is crucial for liver cancer cell viability and tumor growth. The interaction between TRIB2 and PCBP2 also protects liver cancer cells from oxidative damage through the function of glutathione peroxidase 4. Targeting TRIB2 may enhance the effectiveness of therapeutic agents for liver cancer treatment.
CELL DEATH & DISEASE
(2021)
Article
Biochemistry & Molecular Biology
Jin Hwa Cho, Kidae Kim, Sung Ah Kim, Sungryul Park, Bi-Oh Park, Jong-Hwan Kim, Seon-Young Kim, Min Jee Kwon, Myeong Hoon Han, Sung Bae Lee, Byoung Chul Park, Sung Goo Park, Jeong-Hoon Kim, Sunhong Kim
Summary: OTUD5 has been identified as a novel positive regulator of the mTOR complex signaling pathways, playing a role in stabilizing specific proteins to degrade the inhibitory protein DEPTOR of mTOR, affecting physiological phenotypes such as cell size and autophagy. Our results suggest a positive feedback loop between OTUD5 and the mTOR signaling pathway.
CELL DEATH AND DIFFERENTIATION
(2021)
Article
Biochemistry & Molecular Biology
Xin Bu, Xuan Qu, Kai Guo, Xiangliang Meng, Xing Yang, Qike Huang, Wenjie Dou, Lin Feng, Xinxin Wei, Jiwei Gao, Wei Sun, Min Chao, Liying Han, Yaqin Hu, Liangliang Shen, Jian Zhang, Liang Wang
Summary: CD147 overexpression contributes to TMZ resistance in glioma cells through post-translational regulation of Nrf2 expression. Suppression of CD147 expression enhances the inhibitory effect of TMZ on cell survival by inhibiting GSK3 beta/beta-TrCP-dependent Nrf2 degradation and increasing Nrf2-mediated anti-oxidant gene expressions. Targeting CD147/Nrf2 axis may provide a new strategy for the treatment of TMZ resistant gliomas.
INTERNATIONAL JOURNAL OF BIOLOGICAL SCIENCES
(2021)
Article
Oncology
Xuecen Wang, Zhirui Cao, Xin Yue, Tingyu Liu, Gesi Wen, Dongmei Jiang, Weijian Wu, Liyuan Le, Yan Wang, Chengtao Wang, Ziyang Wang, Meng Jin, Meiyan Zhu, Shasha He, Xiaoyue Zhang, Xianzhang Bu, Ran-yi Liu, Zhenwei Peng, Yong Chen
Summary: This study reveals that radiation treatment increases the expression of proteasomal genes in hypopharyngeal cancer cells, and this process is dependent on the induction of the transcription factor NRF1. Furthermore, it was found that inhibiting the proteasome-mediated degradation of DEPTOR protein enhances the sensitivity of hypopharyngeal cancer cells to radiation therapy.
MOLECULAR THERAPY-ONCOLYTICS
(2022)
Article
Biochemistry & Molecular Biology
Fengwu Zhang, Yongchao Zhao, Yi Sun
Summary: USP2 was identified as a new deubiquitylase that stabilizes SKP2 protein by disrupting its interaction with substrates, thereby affecting cell growth regulation. Inactivation of USP2 can shorten SKP2 protein half-life and enhance its ubiquitylation and degradation, but surprisingly, USP2-stabilized SKP2 does not destabilize its substrates p21 and p27. Knockdown or inhibition of USP2 can partially mediate growth suppression through modulation of SKP2 and its substrates.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2021)
Article
Multidisciplinary Sciences
Raed Abu-Dawud, Bhavesh Mistry, Mohamed Rajab, Maha Alanazi, Nadya Al-Yacoub, Junaid Kashir, Falah Almohanna, Dilek Colak, Abdullah M. Assiri
Summary: This study found that disruption of Dcaf17 affects testicular protein homeostasis and transcriptional signature in mice, leading to male infertility.
SCIENTIFIC REPORTS
(2022)
Article
Medicine, Research & Experimental
Yanli Bi, Xiaoyu Chen, Bajin Wei, Linchen Wang, Longyuan Gong, Haomin Li, Xiufang Xiong, Yongchao Zhao
Summary: DEPTOR interacts with and stabilizes ErbB2, promoting proliferation and survival of ErbB2-positive breast cancer cells. Overexpression of DEPTOR is correlated with poorer patient survival, and the membrane localization of DEPTOR may contribute to the oncogenic characteristics of ErbB2.
Article
Cell Biology
Airong Qian, Tzu-Bou Hsieh, M. Moazzem Hossain, Jim J-C Lin, J-P Jin
Summary: Calponin 2 is a crucial protein regulating cell motility-related functions and cell division. Proper expression levels and degradation of calponin 2 play essential roles in normal cytokinesis. PKC phosphorylation-triggered degradation of calponin 2 may determine the rate of cell division.
AMERICAN JOURNAL OF PHYSIOLOGY-CELL PHYSIOLOGY
(2021)
Article
Microbiology
Charlotte A. Stoneham, Simon Langer, Paul D. De Jesus, Jacob M. Wozniak, John Lapek, Thomas Deerinck, Andrea Thor, Lars Pache, Sumit K. Chanda, David J. Gonzalez, Mark Ellisman, John Guatelli
Summary: The HIV-1 accessory protein Vpu modulates membrane protein trafficking and degradation to evade immune surveillance, directing targets to degradation organelles through specific pathways involving a variety of cellular proteins.
Article
Cell Biology
Yanli Bi, Longyuan Gong, Pengyuan Liu, Xiufang Xiong, Yongchao Zhao
Summary: This study reveals a novel mechanism in which nuclear ErbB2 represses the transcription of DEPTOR, leading to activation of the PI3K/AKT/mTOR pathway to inhibit autophagy.
CELL DEATH & DISEASE
(2021)
Article
Biochemistry & Molecular Biology
Jing-Ting Chiou, Yuan-Chin Lee, Liang-Jun Wang, Long-Sen Chang
Summary: This study found that human leukemia U937 cells continuously treated with hydroquinone (HQ) showed reduced sensitivity to BCL2 and BCL2L1 inhibitors. However, the combination of WEHI-539 and ABT-199 or ABT-263 showed synergistic cytotoxicity to U937 and U937/HQ cells. Further investigation revealed that the combined treatment induced autophagy, accelerated beta-TrCP mRNA degradation, and led to NOXA-dependent MCL1 degradation.
CHEMICO-BIOLOGICAL INTERACTIONS
(2022)
Article
Multidisciplinary Sciences
Christopher J. Anderson, Christopher B. Medina, Brady J. Barron, Laura Karvelyte, Tania Love Aaes, Irina Lambertz, Justin S. A. Perry, Parul Mehrotra, Amanda Goncalves, Kelly Lemeire, Gillian Blancke, Vanessa Andries, Farzaneh Ghazavi, Arne Martens, Geert van Loo, Lars Vereecke, Peter Vandenabeele, Kodi S. Ravichandran
Summary: The study demonstrates how nutrients released from apoptotic cells can promote the growth of Enterobacteriaceae and highlights the role of pyruvate formate-lyase-encoding pflB gene in bacterial colonization in various contexts. These findings provide new insights into host-pathogen interactions and have implications for gut inflammation and chemotherapy treatment.
Review
Cell Biology
Elke De Schutter, Ria Roelandt, Franck B. Riquet, Guy Van Camp, Andy Wullaert, Peter Vandenabeele
Summary: The GSDM family consists of six gene clusters with a unique N-terminal domain, capable of executing plasma membrane permeabilization. The activity of GSDME and GSDMD, the most widely expressed and best-studied GSDMs, is directly regulated by protease-and kinase-dependent mechanisms. Evolutionary forces and a unique position of the PJVK gene are associated with complex inner-ear development in vertebrates.
TRENDS IN CELL BIOLOGY
(2021)
Article
Cell Biology
Tom Delanghe, Jon Huyghe, Seungheon Lee, Dario Priem, Samya Van Coillie, Barbara Gilbert, Sze Men Choi, Peter Vandenabeele, Alexei Degterev, Gregory D. Cuny, Yves Dondelinger, Mathieu J. M. Bertrand
Summary: The study reveals that BHA functions as a direct inhibitor of RIPK1 enzymatic activity, protecting cells from necroptosis and apoptosis. This finding suggests new functions of RIPK1 beyond its previously known roles.
CELL DEATH & DISEASE
(2021)
Article
Multidisciplinary Sciences
Klaas Yperman, Anna C. Papageorgiou, Romain Merceron, Steven De Munck, Yehudi Bloch, Dominique Eeckhout, Qihang Jiang, Pieter Tack, Rosa Grigoryan, Thomas Evangelidis, Jelle Van Leene, Laszlo Vincze, Peter Vandenabeele, Frank Vanhaecke, Martin Potocky, Geert De Jaeger, Savvas N. Savvides, Konstantinos Tripsianes, Roman Pleskot, Daniel Van Damme
Summary: This study elucidated the structural and functional roles of the EH domains of the TPC subunit AtEH1/Pan1 in plant Clathrin-mediated endocytosis (CME). The research integrated high-resolution structural information obtained by X-ray crystallography and NMR spectroscopy with all-atom molecular dynamics simulations to provide insights into the function of both EH domains. The study revealed distinct but complementary roles of the EH domains of AtEH/Pan1 in plant CME and connected the internalization of SCAMP5 to the TPLATE complex.
NATURE COMMUNICATIONS
(2021)
Article
Biochemistry & Molecular Biology
Elke De Schutter, Jana Ramon, Benjamin Pfeuty, Caroline De Tender, Stephan Stremersch, Koen Raemdonck, Ken Op de Beeck, Wim Declercq, Franck B. Riquet, Kevin Braeckmans, Peter Vandenabeele
Summary: This study investigates the membrane permeabilizing features of Gasdermin E (GSDME) and its role in regulating secondary necrosis. The results show that GSDME accelerates cell lysis and affects the influx of fluorescently labeled dextrans, while the efflux is independent of GSDME expression. Furthermore, the passage of dextrans is dependent on their molecular weight.
CELLULAR AND MOLECULAR LIFE SCIENCES
(2022)
Article
Multidisciplinary Sciences
Filip Van Hauwermeiren, Nina Van Opdenbosch, Hanne Van Gorp, Nathalia de Vasconcelos, Geert van Loo, Peter Vandenabeele, Thirumala-Devi Kanneganti, Mohamed Lamkanfi
Summary: Bacillus anthracis induces activation of the NLRP3 inflammasome and macrophage apoptosis through TNF and RIPK1 kinase activity, which are key host-pathogen mechanisms in lethal anthrax.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Article
Multidisciplinary Sciences
Farzaneh Ghazavi, Jelle Huysentruyt, Jordy De Coninck, Stephanie Kourula, Sofie Martens, Behrouz Hassannia, Tim Wartewig, Tatyana Divert, Ria Roelandt, Bastian Popper, Andreas Hiergeist, Peter Tougaard, Tom Vanden Berghe, Marie Joossens, Geert Berx, Nozomi Takahashi, Adam Wahida, Peter Vandenabeele
Summary: Apoptosis is not essential for turnover of intestinal epithelial cells, maintenance of barrier function, microbiome, and immune cell composition during homeostasis.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Review
Biochemistry & Molecular Biology
Simon Verdonck, Josephine Nemegeer, Peter Vandenabeele, Jonathan Maelfait
Summary: Cell death, including necroptosis and pyroptosis, is an important part of the antiviral immune response, eliminating virus-infected cells and promoting immune development through the release of inflammatory mediators. Viruses employ evasion mechanisms to suppress these cell death pathways and antagonize host immunity.
TRENDS IN MICROBIOLOGY
(2022)
Article
Cell Biology
Teodora Oltean, Lorena Itati Ibanez, Tatyana Divert, Tine Ysenbaert, Hannelore Van Eeckhoutte, Vera Goossens, Michael Schotsaert, Ken Bracke, Bert Schepens, Jonathan Maelfait, Nozomi Takahashi, Xavier Saelens, Peter Vandenabeele
Summary: RIPK3 partially protects against disease caused by influenza A virus infection in mice. Active vaccination with M2e viral antigen provides protection against IAV, but this protection is lost in Ripk3(-/-) mice.
CELL DEATH & DISEASE
(2022)
Article
Cell Biology
Sofie Martens, Nozomi Takahashi, Gillian Blancke, Niels Vandamme, Hanne Verschuere, Tatyana Divert, Marnik Vuylsteke, Geert Berx, Peter Vandenabeele
Summary: This study investigates the role of MLKL during melanoma initiation and progression. MLKL deficiency in male mice results in a modest reduction of nevi growth rate and infiltration of melanoma cells in the lymph node, while no significant difference is observed in female mice.
CELL DEATH & DISEASE
(2022)
Article
Multidisciplinary Sciences
Samya Van Coillie, Emily Van San, Ines Goetschalckx, Bartosz Wiernicki, Banibrata Mukhopadhyay, Wulf Tonnus, Sze Men Choi, Ria Roelandt, Catalina Dumitrascu, Ludwig Lamberts, Geert Dams, Wannes Weyts, Jelle Huysentruyt, Behrouz Hassannia, Irina Ingold, Suhas Lele, Evelyne Meyer, Maya Berg, Ruth Seurinck, Yvan Saeys, An Vermeulen, Alexander L. N. van Nuijs, Marcus Conrad, Andreas Linkermann, Mohan Rajapurkar, Peter Vandenabeele, Eric Hoste, Koen Augustyns, Tom Vanden Berghe
Summary: The development of multiorgan dysfunction syndrome (MODS) is the most common cause of death in the intensive care unit (ICU). Catalytic iron is associated with ICU mortality and may induce excessive lipid peroxidation, leading to cellular toxicity and multiorgan dysfunction. Blocking lipid peroxidation with a ferrostatin-analogue can protect mice from injury and death in experimental non-septic MODS.
NATURE COMMUNICATIONS
(2022)
Article
Biochemistry & Molecular Biology
Roberto Fernandez-Acosta, Claudia Iriarte-Mesa, Daniel Alvarez-Alminaque, Behrouz Hassannia, Bartosz Wiernicki, Alicia M. Diaz-Garcia, Peter Vandenabeele, Tom Vanden Berghe, Gilberto L. Pardo Andreu
Summary: The use of iron-based polymeric nanoparticles (IONP-GA/PAA) coated with gallic acid and polyacrylic acid has shown to efficiently induce ferroptosis in various cancer cell lines, making it a potential therapeutic strategy for tumor treatment. The ferroptosis-inducing effect of IONP-GA/PAA can be blocked by canonical ferroptosis inhibitors, and these inhibitors also prevent the generation of lipid hydroperoxide promoted by the nanoparticles.
Article
Multidisciplinary Sciences
Richard de Reuver, Simon Verdonck, Evelien Dierick, Josephine Nemegeer, Eline Hessmann, Sadeem Ahmad, Maude Jans, Gillian Blancke, Filip Van Nieuwerburgh, Alexander Botzki, Lars Vereecke, Geert van Loo, Wim Declercq, Sun Hur, Peter Vandenabeele, Jonathan Maelfait
Summary: The RNA-editing enzyme ADAR1 plays an important role in limiting the accumulation of immunostimulatory dsRNA. Reduced ADAR1 activity can lead to severe inflammatory diseases, while complete loss of ADAR1 activity is embryonically lethal and causes autoinflammation. ADAR1 not only prevents overactivation of MDA5 and PKR, but also inhibits the spontaneous activation of ZBP1.
Article
Multidisciplinary Sciences
Bartosz Wiernicki, Sophia Maschalidi, Jonathan Pinney, Sandy Adjemian, Tom Vanden Berghe, Kodi S. Ravichandran, Peter Vandenabeele
Summary: Ferroptosis, a form of cell death characterized by iron accumulation and lipid peroxidation, has lower immunogenicity compared to other cell death modalities, inhibiting the maturation and antigen cross-presentation of immune cells and hence weakening the anti-tumor immune response.
NATURE COMMUNICATIONS
(2022)
Article
Oncology
Teodora Oltean, Lien Lippens, Kelly Lemeire, Caroline De Tender, Marnik Vuylsteke, Hannelore Denys, Katrien Vandecasteele, Peter Vandenabeele, Sandy Adjemian
Summary: Irradiation can trigger different cellular responses, including immunogenic cell death. This study aims to determine whether intra-tumoral immunogenic cell death markers can predict the outcomes of patients with cervical cancer.
FRONTIERS IN ONCOLOGY
(2022)