Article
Biology
Min Xie, Ren Hui Chia, Dan Li, Fanny Xueting Teo, Christian Krueger, Kanaga Sabapathy
Summary: The transcription factor c-Jun plays a pro-fibrogenic role in hepatocytes and KCs that functionally interact to regulate liver fibrosis. Deletion of c-Jun in both hepatocytes and KCs reduces fibrosis and cytokine gene expression, but does not affect the resolution phase after fibrotic injury.
LIFE SCIENCE ALLIANCE
(2021)
Article
Cell Biology
Michael Keith Kullmann, Fragka Pegka, Christian Ploner, Ludger Hengst
Summary: In addition to serving as a CDK inhibitor and tumor suppressor, p57 may also promote tumor growth by activating the proto-oncoprotein c-Jun.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2021)
Article
Medicine, Research & Experimental
Philipp Novoszel, Martin Holcmann, Gabriel Stulnig, Cristiano De Sa Fernandes, Victoria Zyulina, Izabela Borek, Markus Linder, Alexandra Bogusch, Barbara Drobits, Thomas Bauer, Carmen Tam-Amersdorfer, Patrick M. Brunner, Georg Stary, Latifa Bakiri, Erwin F. Wagner, Herbert Strobl, Maria Sibilia
Summary: This study found that c-Jun/AP-1 protein regulates CCL2 and IL-23 production in DCs following TLR7 activation, affecting psoriasis-like skin inflammation. The expression of CCL2 and IL-23 in human psoriatic skin co-localize with c-Jun in type-2/inflammatory DCs, and inhibition of JNK-AP-1 can reduce the expression of these targets in TLR7/8-stimulated human DCs.
EMBO MOLECULAR MEDICINE
(2021)
Article
Virology
Yuling Tang, Guanghui Yang, Yuxiang Li, Ming Wang, Gebin Li, Yanxin Hu
Summary: SP600125 treatment reduced pulmonary inflammatory response and lung injury, decreased viral load, and increased survival rate of H1N1-infected mice. The study confirmed the crucial role of c-Jun N terminal kinase in H1N1 virus replication and inflammatory responses.
ARCHIVES OF VIROLOGY
(2021)
Article
Biochemistry & Molecular Biology
Blessy M. Suresh, Yuquan Tong, Daniel Abegg, Alexander Adibekian, Jessica L. Childs-Disney, Matthew D. Disney
Summary: This study investigates the factors affecting the degradation of two cancer-associated RNA targets and explores how structural features can be leveraged to program selective small-molecule degradation. The findings have important implications for the development of chemical probes and potential lead medicines targeting RNA.
ACS CHEMICAL BIOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Tetsuaki Miyake, John C. McDermott
Summary: This study reveals that the proto-oncogene c-Jun can be targeted to the nucleolus, and its basic domain contains a unique motif that determines nucleolar localization. While partners such as Fra2 do not co-localize with c-Jun in the nucleolus. A point mutation can result in loss of nucleolar targeting for c-Jun, while its nuclear localization remains intact.
Article
Oncology
Hao Li, Taoran Zhou, Yue Zhang, Hengyi Jiang, Jing Zhang, Zichun Hua
Summary: RuvBL1 is identified as a repressor of c-Jun/AP-1 activity leading to TRAIL resistance in lung cancer cells. Silencing RuvBL1 can sensitize resistant cells to TRAIL, while high expression of RuvBL1 inversely related to low c-Jun is associated with a poor overall prognosis in lung cancer patients.
FRONTIERS IN ONCOLOGY
(2021)
Article
Medicine, General & Internal
Hong Weng, Kang-Ping Xiong, Wang Wang, Kai-Yu Qian, Shuai Yuan, Gang Wang, Fang Yu, Jun Luo, Meng-Xin Lu, Zhong-Hua Yang, Tao Liu, Xing Huang, Hang Zheng, Xing-Huan Wang
Summary: The study identified aspartoacylase (ASPA) as a novel inhibitor of prostate cancer (PCa) progression. ASPA was down-regulated in PCa tissue samples and its decreased expression was associated with patients' prognosis. ASPA was found to interact with and inhibit the phosphorylation of the LYN protein and its downstream targets, playing an important role in PCa development. These findings provide new insights into the tumor-suppressive function of ASPA in PCa and suggest its potential as a prognostic biomarker and therapeutic target.
MILITARY MEDICAL RESEARCH
(2023)
Article
Multidisciplinary Sciences
Swantje Christin Hager, Catarina Dias, Stine Lauritzen Sonder, Andre Vidas Olsen, Isabelle da Piedade, Anne Sofie Busk Heitmann, Elena Papaleo, Jesper Nylandsted
Summary: Plasma membrane repair mechanisms are quickly activated post-injury, leading to rapid membrane resealing and preventing cell death. A genome-wide study on breast cancer cells exposed to injury revealed a time-dependent transcriptional response marked by immediate-early response genes, specific MAPK cascades, and inflammatory and immune pathways induction, highlighting a conserved stress and immunogenic response to plasma membrane injury.
SCIENTIFIC REPORTS
(2021)
Article
Cell Biology
Omeed Darweesh, Eman Al-Shehri, Hugo Falquez, Joachim Lauterwasser, Frank Edlich, Rajnikant Patel
Summary: The binding of activated Cdk1 with pro-apoptotic proteins Bax and Bak plays a crucial role in SAC-induced apoptosis, facilitating the phosphorylation of mitochondria and cell death.
JOURNAL OF CELL SCIENCE
(2021)
Article
Biology
Stefanie Dichtl, David E. Sanin, Carolin K. Koss, Sebastian Willenborg, Andreas Petzold, Maria C. Tanzer, Andreas Dahl, Agnieszka M. Kabat, Laura Lindenthal, Leonie Zeitler, Sabrina Satzinger, Alexander Strasser, Matthias Mann, Axel Roers, Sabine A. Eming, Karim C. El Kasmi, Edward J. Pearce, Peter J. Murray
Summary: Anti-TNF therapies can protect against chronic diseases by modulating the balance of macrophage activity, specifically regulating components of tissue and reparative M2 macrophages.
LIFE SCIENCE ALLIANCE
(2022)
Article
Biochemistry & Molecular Biology
Baowen Zhuo, Qifan Zhang, Tingyan Xie, Yidan Wang, Zhengliang Chen, Daming Zuo, Bo Guo
Summary: Regulatory T (Treg) cells in human tumors exhibit more potent immunosuppressive activity than peripheral blood Treg cells (PBTRs), which impairs the induction of effective antitumor immunity. This study explores the epigenetic profiles of tumor-infiltrating Treg cells (TITRs) and identifies functional regulatory elements. The researchers found global differences in chromatin accessibility and enhancer landscapes between TITRs and PBTRs, as well as two types of active enhancer formation in TITRs. They also discovered that the AP-1 family motifs are enriched at the enhancer regions of TITRs and validated the role of c-Jun in regulating signature genes of TITRs and Treg cell activation. The findings provide insights into the mechanism of AP-1-mediated activation of TITRs and may contribute to the development of new therapeutic strategies for liver cancer treatment.
CELLULAR AND MOLECULAR LIFE SCIENCES
(2023)
Article
Endocrinology & Metabolism
Yu Ting Ong, Jorge Andrade, Max Armbruster, Chenyue Shi, Marco Castro, Ana S. H. Costa, Toshiya Sugino, Guy Eelen, Barbara Zimmermann, Kerstin Wilhelm, Joseph Lim, Shuichi Watanabe, Stefan Guenther, Andre Schneider, Francesca Zanconato, Manuel Kaulich, Duojia Pan, Thomas Braun, Holger Gerhardt, Alejo Efeyan, Peter Carmeliet, Stefano Piccolo, Ana Rita Grosso, Michael Potente
Summary: Ong et al. report on the intersection of YAP/TAZ and mTORC1 signalling in endothelial cells, showing their role in regulating nutrient acquisition and vascular growth. YAP/TAZ promote angiogenesis by stimulating the import of amino acids and other essential nutrients, leading to mTORC1 activation. This study highlights the importance of coordinated nutrient fluxes in the vasculature.
Article
Immunology
Yinna Song, Yanyu Guo, Xiaoyang Li, Ruiqi Sun, Min Zhu, Jingxuan Shi, Zheng Tan, Lilin Zhang, Jinhai Huang
Summary: In PRRSV-infected cells, the up-regulation of RBM39 and down-regulation of inflammatory cytokines were observed, suggesting a potential role of RBM39 in promoting PRRSV proliferation. The study also revealed the mechanism of RBM39 in altering c-Jun phosphorylation and nucleocytoplasmic translocation, which may contribute to immune escape mechanism of PRRSV infection.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Cardiac & Cardiovascular Systems
Jing Tan, Wei Gao, Wanchao Yang, Xianzhang Zeng, Linlin Wang, Xiaoguang Cui
Summary: JNK1 exacerbates ischemia-reperfusion injury in lung transplantation, while JNK2 alleviates it. JNK1 silencing attenuates lung graft dysfunction by inhibiting inflammation and apoptosis.
JOURNAL OF THORACIC AND CARDIOVASCULAR SURGERY
(2021)
Article
Multidisciplinary Sciences
Monika M. Gladka, Arwa Kohela, Bas Molenaar, Danielle Versteeg, Lieneke Kooijman, Jantine Monshouwer-Kloots, Veerle Kremer, Harmjan R. Vos, Manon M. H. Huibers, Jody J. Haigh, Danny Huylebroeck, Reinier A. Boon, Mauro Giacca, Eva van Rooij
Summary: ZEB2 is a beneficial transcription factor that induces cardioprotective effects in a subset of stressed cardiomyocytes. Therapeutic delivery of ZEB2 to cardiomyocytes prevents cardiac dysfunction after ischemic damage and promotes the activation of pro-angiogenic signals.
NATURE COMMUNICATIONS
(2021)
Article
Cardiac & Cardiovascular Systems
Willeke de Haan, Wouter Dheedene, Katerina Apelt, Sofiane Decombas-Deschamps, Stefan Vinckier, Stefaan Verhulst, Andrea Conidi, Thomas Deffieux, Michael W. Staring, Petra Vandervoort, Ellen Caluwe, Marleen Lox, Inge Mannaerts, Tsuyoshi Takagi, Joris Jaekers, Geert Berx, Jody Haigh, Baki Topal, An Zwijsen, Yujiro Higashi, Leo A. van Grunsven, Wilfred F. J. van IJcken, Eskeatnaf Mulugeta, Mickael Tanter, Franck P. G. Lebrin, Danny Huylebroeck, Aernout Luttun
Summary: This study demonstrated the specific role of Zeb2 in liver endothelial cells, showing that Zeb2 deficiency leads to significant changes in gene expression related to angiogenesis and potential promotion of endothelial dedifferentiation. Furthermore, Zeb2 regulates LSEC-HSC communication and HSC activation to maintain vascular structure and inhibit liver fibrosis.
CARDIOVASCULAR RESEARCH
(2022)
Article
Multidisciplinary Sciences
Chenxu Yan, Tianshu Zeng, Kailun Lee, Max Nobis, Kim Loh, Luoning Gou, Zefeng Xia, Zhongmin Gao, Mohammed Bensellam, Will Hughes, Jackie Lau, Lei Zhang, Chi Kin Ip, Ronaldo Enriquez, Hanyu Gao, Qiao-Ping Wang, Qi Wu, Jody J. Haigh, D. Ross Laybutt, Paul Timpson, Herbert Herzog, Yan-Chuan Shi
Summary: Blocking Y1 receptors in peripheral tissues using selective antagonists can reduce weight gain, decrease fat mass, and improve glucose metabolism, suggesting a potential safer and more effective treatment for diet-induced obesity.
NATURE COMMUNICATIONS
(2021)
Article
Cell & Tissue Engineering
Christopher Gribben, Christopher Lambert, Hendrik A. Messal, Ella-Louise Hubber, Chloe Rackham, Ian Evans, Harry Heimberg, Peter Jones, Rocio Sancho, Axel Behrens
Summary: Ductal cells have been identified as a source of adult beta cell neogenesis, contributing to the beta cell population over time. The expression of Ngn3 in ductal cells plays a role in adult beta cell neogenesis, potentially impacting diabetes onset. Additionally, single-cell RNA sequencing revealed duct-derived somatostatin-expressing cells gave rise to beta cells.
Article
Medicine, Research & Experimental
Jose Gonzalez-Martinez, Andrzej W. Cwetsch, Diego Martinez-Alonso, Luis R. Lopez-Sainz, Jorge Almagro, Anna Melati, Jesus Gomez, Manuel Perez-Martinez, Diego Megias, Jasminka Boskovic, Javier Gilabert-Juan, Osvaldo Grana-Castro, Alessandra Pierani, Axel Behrens, Sagrario Ortega, Marcos Malumbres
Summary: The study reveals that defects in certain genes during development can lead to mild MCPH symptoms, while the lack of centrosome or centriole regulators can cause chromosomal instability in neural progenitor cells.
Article
Medicine, Research & Experimental
E. Josue Ruiz, Linxiang Lan, Markus Elmar Diefenbacher, Eva Madi Riising, Clive Da Costa, Atanu Chakraborty, Joerg D. Hoeck, Bradley Spencer-Dene, Gavin Kelly, Jean-Pierre David, Emma Nye, Julian Downward, Axel Behrens
Summary: In a mouse model of K-RasG12D-induced lung adenocarcinoma, deletion or mutation of c-Jun unexpectedly increased lung tumor burden, while the Jun family member JunD was found to be crucial in JNK signaling and Ras-induced lung cancer in the absence of c-Jun.
Article
Biochemistry & Molecular Biology
Huafu Li, Chunming Wang, Linxiang Lan, Leping Yan, Wuguo Li, Ian Evans, E. Josue Ruiz, Qiao Su, Guangying Zhao, Wenhui Wu, Haiyong Zhang, Zhijun Zhou, Zhenran Hu, Wei Chen, Joaquim M. Oliveira, Axel Behrens, Rui L. Reis, Changhua Zhang
Summary: In this study, the researchers investigated the mechanism of oxaliplatin resistance in gastric cancer using in vitro human gastric cancer organoids and oxaliplatin-resistant cell lines, as well as in vivo tumorigenicity experiments. They found that CD133+ stem cell-like cells are the main subpopulation associated with resistance, and that the gene PARP1 plays a central role in mediating this resistance. The researchers discovered that PARP1 can effectively repair DNA damage caused by oxaliplatin by activating the base excision repair pathway, leading to the development of drug resistance. They also found that CD133+ cells exhibit increased expression of the mRNA modification N6-methyladenosine (m6A) and its writer METTL3, which enhances the stability of PARP1 and contributes to its DNA damage repair ability. Overall, this study demonstrates that m6A methyltransferase METTL3 promotes oxaliplatin resistance in CD133+ gastric cancer stem cells by increasing PARP1 mRNA stability and base excision repair activity.
CELLULAR AND MOLECULAR LIFE SCIENCES
(2022)
Article
Biochemistry & Molecular Biology
Matthew R. J. Mason, Susan van Erp, Kim Wolzak, Axel Behrens, Gennadij Raivich, Joost Verhaagen
Summary: The regeneration-associated gene expression program is crucial for axon re-growth in injured peripheral neurons. Jun, a transcription factor, plays an important role in regulating this program by upregulating gene expression and promoting cell regeneration while inhibiting plasticity response.
HUMAN MOLECULAR GENETICS
(2022)
Article
Multidisciplinary Sciences
Jessica K. Nelson, May Zaw Thin, Theodore Evan, Steven Howell, Mary Wu, Bruna Almeida, Nathalie Legrave, Duco S. Koenis, Gabriela Koifman, Yoichiro Sugimoto, Miriam Llorian Sopena, James MacRae, Emma Nye, Michael Howell, Ambrosius P. Snijders, Andreas Prachalias, Yoh Zen, Debashis Sarker, Axel Behrens
Summary: This study reveals that the deubiquitinating enzyme USP25 promotes growth and survival of pancreatic ductal adenocarcinoma (PDAC) by stabilizing and regulating the transcriptional activity of HIF-1 protein. PDAC is characterized by a severely hypoxic microenvironment, and inhibition of USP25 impairs HIF-1 activity and induces cell death in the tumor core. The USP25/HIF-1α axis may be a potential therapeutic target for PDAC.
NATURE COMMUNICATIONS
(2022)
Article
Multidisciplinary Sciences
Linxiang Lan, Theodore Evan, Huafu Li, Aasia Hussain, E. Josue Ruiz, May Zaw Thin, Rute M. M. Ferreira, Hari Ps, Eva M. Riising, Yoh Zen, Jorge Almagro, Kevin W. Ng, Pablo Soro-Barrio, Jessica Nelson, Gabriela Koifman, Joana Carvalho, Emma L. Nye, Yulong He, Changhua Zhang, Anguraj Sadanandam, Axel Behrens
Summary: This study identifies BMP inhibitor GREM1 as a key regulator of cellular heterogeneity in pancreatic cancer. Continuous activity of GREM1 is required to maintain the stability of the epithelial PDAC subpopulations, while high activity of GREM1 can revert the mesenchymal fate of PDAC cells. By inhibiting the expression of epithelial-mesenchymal transition transcription factors, GREM1 restricts the epithelial-mesenchymal plasticity of pancreatic cancer cells.
Article
Oncology
Aissa Benyoucef, Katharina Haigh, Andrew Cuddihy, Jody J. Haigh
Summary: ETP-ALL is a high-risk subtype of T cell acute lymphoblastic leukemia that often relapses after conventional chemotherapy. In this study, the authors discovered the novel involvement of ZEB2/LSD1 complexes in repressing the intrinsic apoptosis pathway and identified BIM as a major driver for ETP-ALL survival. Treatment with LSD1 inhibitors restored the expression of BIM and, when combined with other inhibitors, reversed the resistance of ETP-ALL to LSD1 inhibitors, leading to inhibited growth and enhanced differentiation of ETP-ALL cells.
Review
Oncology
Matthew S. Gillespie, Ciara M. Ward, Clare C. Davies
Summary: Cancer stem cells (CSCs) play a crucial role in cancer development, progression, metastasis, and relapse. They are highly drug resistant due to enhanced DNA repair efficiency. This review discusses the mechanisms of CSC drug resistance and strategies for targeting the DNA damage response to improve cancer treatment efficacy.
Article
Biology
Carlos Farkas, Antonia Recabal, Andy Mella, Daniel Candia-Herrera, Maryori Gonzalez Olivero, Jody Jonathan Haigh, Estefania Tarifeno-Saldivia, Teresa Caprile
Summary: This study developed a genome-guided transcriptome annotation pipeline that integrates various bioinformatics approaches to accurately annotate the transcriptome and identify new genes and homologous species.
Review
Oncology
Jorge Almagro, Hendrik A. Messal, Alberto Elosegui-Artola, Jacco van Rheenen, Axel Behrens
Summary: The 3D architecture of tissues bearing tumors has significant impacts on the mechanical microenvironment of cancer, the accessibility of stromal cells, and the routes of invasion. Various forces from cancer cells, host tissue, and the molecular and cellular microenvironment modulate the morphology and malignant potential of the tumor through mechanical, biochemical, genetic, and epigenetic cues. Recent studies have revealed how tissue architecture influences cancer biology and progression.
Review
Oncology
Jorge Almagro, Hendrik A. Messal, May Zaw Thin, Jacco van Rheenen, Axel Behrens
Summary: The visualization of whole organs and organisms through tissue clearing and fluorescence volumetric imaging has revolutionized the way we study biological samples, particularly in tumor research and cancer diagnostics.
NATURE REVIEWS CANCER
(2021)