Article
Biochemistry & Molecular Biology
Anna Geueke, Giada Mantellato, Florian Kuester, Peter Schettina, Melanie Nelles, Jens Michael Seeger, Hamid Kashkar, Catherin Niemann
Summary: This study reveals the impact of Bcl-2 on the function of hair follicle stem cells, maintaining the homeostasis and regeneration of stem cells by controlling the apoptosis response, which may also suppress carcinogenesis.
Article
Anatomy & Morphology
Yaxi Zhu, Shuai Zhao, Lan Xiao, Yongbin Wu, Qianlu Wang, Shijun He, Sichuang Tan, Sipin Tan
Summary: This study identified the increased expression of Dp71 in ischemia-reperfusion injured rat hearts and its protective role against H2O2-induced apoptosis in H9c2 cells. The upregulation of Bcl-2 expression and FAK and p65 phosphorylation may contribute to the cardiac protective effects of Dp71.
Article
Medicine, Research & Experimental
Elisabetta Valentini, Simona D'Aguanno, Marta Di Martile, Camilla Montesano, Virginia Ferraresi, Alexandros Patsilinakos, Manuela Sabatino, Lorenzo Antonini, Martina Chiacchiarini, Sergio Valente, Antonello Mai, Gianni Colotti, Rino Ragno, Daniela Trisciuoglio, Donatella Del Bufalo
Summary: Bcl-2 family anti-apoptotic proteins play a significant role in cancer, and finding new molecules targeting these proteins has therapeutic potential. Through virtual screening and experimental validation, IS20 and IS21 were identified as compounds that can inhibit the activity of Bcl-2 family proteins and have anti-proliferative and pro-apoptotic effects on various tumors.
Review
Biochemistry & Molecular Biology
Hae-Seul Choi, Kwang-Hyun Baek
Summary: Apoptosis is a structured cell death process involving cell morphology and biochemical changes, and the ubiquitin-proteasome system regulates the protein levels. Targeting UPS enzymes and controlling proteasomal degradation of apoptotic proteins could be a unique approach for cancer treatment.
CELLULAR AND MOLECULAR LIFE SCIENCES
(2022)
Article
Chemistry, Medicinal
Zhenwei Zhang, Lijun Bai, Linghui Hou, Hongguang Deng, Shenglin Luan, Dan Liu, Min Huang, Linxiang Zhao
Summary: This review focuses on recent advances in the discovery of novel apoptosis inducers targeting Bcl-2 anti-apoptotic proteins, aiming to overcome existing therapeutic limitations, and introduces strategies and advanced technologies in drug design and optimization.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2022)
Review
Oncology
Megan Jung, Indy Bui, Benjamin Bonavida
Summary: Understanding the gene products that make cancer cells resistant is beneficial in developing new drugs that inhibit resistant factors. One factor controlling the resistance in cancer cells is the transcription factor Yin Yang 1 (YY1). Inhibiting YY1 can restore sensitivities to cytotoxic therapies and allow for cancer cells to respond to treatments.
Article
Biochemistry & Molecular Biology
Pan Pan, Weiwei Ge, Zhiwei Lei, Wei Luo, Yuqing Liu, Zhanwen Guan, Lumiao Chen, Zhenyang Yu, Miaomiao Shen, Dingwen Hu, Qi Xiang, Wenbiao Wang, Pin Wan, Mingfu Tian, Yang Yu, Zhen Luo, Xulin Chen, Heng Xiao, Qiwei Zhang, Xujing Liang, Xin Chen, Yongkui Li, Jianguo Wu
Summary: A study reveals that SARS-CoV-2 employs a distinctive anti-apoptotic mechanism through its N protein to suppress cell apoptosis, thereby promoting viral replication. This explains why SARS-CoV-2 can effectively replicate in asymptomatic individuals and indicates a risk of enhanced coinfection with other viruses.
SIGNAL TRANSDUCTION AND TARGETED THERAPY
(2023)
Article
Biology
James M. Pemberton, Dang Nguyen, Elizabeth J. Osterlund, Wiebke Schormann, Justin P. Pogmore, Nehad Hirmiz, Brian Leber, David W. Andrews
Summary: The anti-apoptotic protein PUMA resists displacement by BH3 mimetics through its binding with both the BH3 motif and a novel binding site within the carboxyl-terminal sequence (CTS). Understanding this resistance mechanism will aid in the design of more effective anti-apoptotic protein inhibitors.
Article
Chemistry, Medicinal
Jaemyun Kim, Seungwon Ji, Jin-Young Lee, Jean Lorquin, Barbora Orlikova-Boyer, Claudia Cerella, Aloran Mazumder, Florian Muller, Mario Dicato, Olivier Detournay, Marc Diederich
Summary: Palytoxin can induce cancer cell death at low picomolar concentrations without toxicity to normal cells. The mechanism involves downregulation of antiapoptotic proteins and upregulation of proteasomal enzymatic activity. Protein phosphatase 2A plays a critical role in the induction of apoptosis by palytoxin. Palytoxin also shows strong inhibitory effects on leukemia and tumor formation in vivo.
Article
Agriculture, Dairy & Animal Science
Reshma S. Raj, D. N. Das, S. Mondal, M. Ashokan, Lakshmi Narasimha Thota, T. Karuthadurai, Nikhil Kumar J. Tej, Kerekoppa P. Ramesha
Summary: This study aimed to analyze the expression of pro-apoptotic BAX and anti-apoptotic BCL-2 genes on lactation performance in Bos indicus and HF crossbred cows during early lactation. The results showed that BCL-2 gene promotes milk production while BAX gene opposes milk production. Bos indicus cows are more sensitive to apoptosis compared to HF crossbreds.
ANIMAL BIOTECHNOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Louise E. King, Ricardo Rodriguez-Enriquez, Robert Pedley, Charlotte E. L. Mellor, Pengbo Wang, Egor Zindy, Michael R. H. White, Keith Brennan, Andrew P. Gilmore
Summary: Mitochondrial priming, an important process in regulating cell apoptosis, is closely related to the retrotranslocation dynamics of Bcl-XL. This study reveals that the binding of Bcl-XL to its BH3-only partners inhibits its retrotranslocation, leading to accumulation of protein complexes carrying priming on mitochondria. Additionally, heterogeneity in priming between cells within a population is found, which predicts their subsequent response to pro-apoptotic signals.
CELL DEATH AND DIFFERENTIATION
(2022)
Article
Immunology
Zhenjie Cao, Xin Yang, Tao Li, Zhiru Liu, Pengfei Li, Yongcan Zhou, Yun Sun
Summary: TroBcl2, an anti-apoptotic regulator, was cloned and its role in apoptosis was investigated in this study. It was found that TroBcl2 was widely distributed in various tissues and its expression was upregulated after LPS stimulation. Functional experiments demonstrated that TroBcl2 inhibits apoptosis by reducing mitochondrial membrane potential loss, decreasing DNA fragmentation, preventing cytochrome c release into the cytoplasm, and reducing caspase 3 and caspase 9 activations.
FRONTIERS IN IMMUNOLOGY
(2023)
Article
Chemistry, Multidisciplinary
Liqiang Zhou, Caihong Dong, Li Ding, Wei Feng, Luodan Yu, Xinwu Cui, Yu Chen
Summary: This study developed a nano-sensitizer system that simultaneously encapsulated ferumoxytol to induce dual ferroptosis/apoptosis pathways by SDT. Ferumoxytol delivers excessive iron into cancer cells, leading to tumor metabolic rewiring and enhanced sensitivity to SDT-induced cell apoptosis. The modulation of ferroptosis checkpoints through ferritinophagy by SDT improves ferroptosis sensitivity and achieves synergistic tumor suppression.
Article
Biochemistry & Molecular Biology
Jonas Schroer, Davide Warm, Federico De Rosa, Heiko J. Luhmann, Anne Sinning
Summary: During early brain development, the BAX/BCL-2 pathway plays a role in regulating cortical neuron removal, with electrical activity serving as a set point of regulation. The upregulation of BAX and downregulation of BCL-2 during the first postnatal week result in a high BAX/BCL-2 ratio, contributing to neuronal death rates. Pharmacological blockade of activity leads to upregulation of Bax, while elevated activity leads to increased BCL-2 expression, indicating the modulation of BAX/BCL-2 expression by electrical activity.
CELLULAR AND MOLECULAR LIFE SCIENCES
(2023)
Article
Biochemistry & Molecular Biology
Vijay Kumar Veena, Ahana Roy Choudhury, Adhikesavan Harikrishnan
Summary: A newly synthesized 4H-chromene carbonitrile derivative was found to strongly interact with Bcl-2 and Bax proteins, leading to downregulation of these antiapoptotic proteins and induction of apoptosis in leukemic cells. The compound showed potential as an inhibitor of antiapoptotic machinery and demonstrated selective inhibition towards certain target proteins essential for cancer cell survival.
JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS
(2022)
Article
Immunology
Li Sun, Wenjie Zhang, Lin Zhao, Yanfang Zhao, Fengge Wang, Andrew M. Lew, Yuekang Xu
Summary: The correlation between infections and vascular autoinflammatory diseases has long been recognized, but the immunological basis of healthy vasculatures that predispose to subsequent vascular autoimmunity during inflammation is not well characterized. This study investigated the immune cells in healthy vascular tissues and found a comprehensive set of immune cells with a higher proportion of innate components. Systemic inflammation eroded the immunotolerant state of vascular tissues, leading to upregulation of proinflammatory cytokines and enhanced antigen presentation by vascular dendritic cells (DCs), ultimately leading to vascular destruction. Different vascular DC subsets had selective effects, with monocyte-derived DCs being potent cytokine producers and B-cell activators, and conventional DCs, particularly cDC1, being efficient at presenting antigens to stimulate T cells.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Oncology
Saketh S. Dinavahi, Yu-Chi Chen, Kishore Punnath, Arthur Berg, Meenhard Herlyn, Momeneh Foroutan, Nicholas D. Huntington, Gavin P. Robertson
Summary: The targeting of the AKT/WEE1 pathways to induce p53 activation is a novel and effective approach to inhibit tumor development. This study shows that this approach can enhance tumor immunogenicity, induce immunogenic cell death, and recruit immune cells in the tumor microenvironment, resulting in tumor regression.
CANCER IMMUNOLOGY RESEARCH
(2022)
Article
Oncology
Pierre-Louis Bernard, Rebecca Delconte, Sonia Pastor, Vladimir Laletin, Cathy Costa Da Silva, Armelle Goubard, Emmanuelle Josselin, Remy Castellano, Adrien Krug, Julien Vernerey, Raynier Devillier, Daniel Olive, Els Verhoeyen, Eric Vivier, Nicholas D. Huntington, Jacques Nunes, Geoffrey Guittard
Summary: This study investigates the impact of targeting an inhibiting protein called CISH in natural killer (NK) cells on their functions and antitumor properties. The results show that CISH deletion enhances NK cell activation and killing abilities, while limiting NK cell exhaustion. Furthermore, CISH deletion optimizes NK cell accumulation in tumors and improves the effectiveness of antitumor responses. Therefore, CISH has been validated as a potential therapeutic target to enhance NK cell immunotherapy.
JOURNAL FOR IMMUNOTHERAPY OF CANCER
(2022)
Article
Immunology
Wayne J. Hawthorne, Evelyn J. Salvaris, Yi Vee Chew, Heather Burns, Joanne Hawkes, Helen Barlow, Min Hu, Andrew M. Lew, Mark B. Nottle, Philip J. O'Connell, Peter J. Cowan
Summary: Genetically modified pig donors, combined with immunosuppression, can provide long-term cure and excellent graft survival in diabetic baboon models.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Immunology
Adam K. Wade-Vallance, Zhiyong Yang, Jeremy B. Libang, Marcus J. Robinson, David M. Tarlinton, Christopher D. C. Allen
Summary: Wade-Vallance et al. demonstrate that the binding of antigen or antibody to the B cell receptor triggers apoptosis in IgE plasma cells. This mechanism is relevant to allergic disease and its treatment through endogenous IgE regulation.
JOURNAL OF EXPERIMENTAL MEDICINE
(2023)
Article
Immunology
Hesham D. D. Abdulla, Raed Alserihi, Christoffer Flensburg, Waruni Abeysekera, Meng-Xiao Luo, Daniel H. D. Gray, Xiaodong Liu, Gordon K. K. Smyth, Warren S. S. Alexander, Ian J. J. Majewski, Matthew P. P. McCormack
Summary: Abdulla et al. demonstrate that the LMO2 transcription factor promotes the development of T-lymphoblastic leukemia by inhibiting thymocyte competition in a transgenic mouse model.
JOURNAL OF EXPERIMENTAL MEDICINE
(2023)
Article
Cell Biology
Timothy Patton, Zhe Zhao, Xin Yi Lim, Eleanor Eddy, Huimeng Wang, Adam G. Nelson, Bronte Ennis, Sidonia B. G. Eckle, Michael N. T. Souter, Troi J. Pediongco, Hui-Fern Koay, Jian-Guo Zhang, Tirta M. Djajawi, Cynthia Louis, Najoua Lalaoui, Nicolas Jacquelot, Andrew M. Lew, Daniel G. Pellicci, James McCluskey, Yifan Zhan, Zhenjun Chen, Kate E. Lawlor, Alexandra J. Corbett
Summary: Cell death mechanisms in T lymphocytes vary depending on their developmental stage, cell subset, and activation status. However, the cell death control mechanisms of mucosal-associated invariant T (MAIT) cells, a specialized T cell population, are not well understood. In this study, it was found that MAIT cells express high levels of key necroptotic machinery, RIPK3 and MLKL proteins. Surprisingly, the loss of RIPK3, but not MLKL or caspase-8, specifically increased the abundance of MAIT cells in various organs, indicating a cell-intrinsic regulation of MAIT cell accumulation by RIPK3 signaling.
CELL DEATH & DISEASE
(2023)
Article
Cell Biology
Lucille C. Rankin, Katherine A. Kaiser, Kenia de los Santos-Alexis, Heekuk Park, Anne-Catrin Uhlemann, Nicholas Arpaia, Daniel H. D. Gray
Summary: Micronutrient deficiency is a leading cause of global diseases. This study reveals that a deficiency in dietary tryptophan (Trp) alters the intestinal microbiome and the immune response, resulting in changes to the Treg cell population. Dietary Trp deficiency leads to the expansion of RORgt+ Treg cells and the loss of Gata3+ Tregs, which can be restored by providing the AhR ligand indole-3-carbinol. These findings emphasize the crucial role of immune-microbiome crosstalk in regulating Treg homeostasis during nutrient deficiency.
Article
Cell Biology
Lizeth G. Meza Guzman, Craig D. Hyland, Grace M. Bidgood, Evelyn Leong, Zihan Shen, Wilford Goh, Jai Rautela, James E. Vince, Sandra E. Nicholson, Nicholas D. Huntington
Summary: The clinical development of NK cell-mediated immunotherapy is a significant milestone in cancer treatment, but improving NK cell persistence and overcoming tumor microenvironment suppression are challenges. This study explores the role of CD45 in NK cell homeostasis and shows that CD45 deficiency does not enhance NK cell persistence, but instead results in a developmental defect. Inhibiting CD45 in progenitor or stem cell populations may improve the yield of in vitro generated NK cells for adoptive therapy.
IMMUNOLOGY AND CELL BIOLOGY
(2023)
Article
Immunology
Nicholas D. Huntington
Summary: IRF4 is necessary for the differentiation of T cells, B cells, and some myeloid cells. A recent study reveals that IRF4 is upregulated after natural killer (NK) cell activation and is essential for the differentiation and expansion of virus-specific NK cells by regulating nutrient acquisition, including iron uptake.
Editorial Material
Immunology
Zhoujie Ding, David Tarlinton
Summary: BALT, formed in the lung during infancy and declining over childhood, plays a role in localized immune reactions against airway infections, including the production of germinal center-like B cells specific for respiratory pathogens.
Article
Multidisciplinary Sciences
Shuwei Liang, Eric Tran, Xin Du, Jiajun Dong, Harrison Sudholz, Hao Chen, Zihan Qu, Nicholas D. Huntington, Jeffrey J. Babon, Nadia J. Kershaw, Zhong-Yin Zhang, Jonathan B. Baell, Florian Wiede, Tony Tiganis
Summary: In this study, the authors demonstrate that inhibition of PTP1B and PTPN2 in tumor cells and T cells with a small molecule inhibitor represses the growth of immunogenic and cold tumors, and enhances response to anti-PD-1 immunotherapy without promoting immune-related toxicities.
NATURE COMMUNICATIONS
(2023)
Article
Immunology
Shengbo Zhang, Jai Rautela, Naiara G. Bediaga, Tatiana B. Kolesnik, Yue You, Junli Nie, Laura F. Dagley, Justin Bedo, Hanqing Wang, Li Sun, Robyn Sutherland, Elliot Surgenor, Nadia Iannarella, Rhys Allan, Fernando Souza-Fonseca-Guimaraes, Yi Xie, Qike Wang, Yuxia Zhang, Yuekang Xu, Stephen L. Nutt, Andrew M. Lew, Nicholas D. Huntington, Sandra E. Nicholson, Michael Chopin, Yifan Zhan
Summary: The cytokine GM-CSF can differentiate monocytes into macrophages with opposing functions, proinflammatory M1-like and immunosuppressive M2-like. In this study, it was found that the protein CIS plays a critical role in the GM-CSF signaling pathway, and deficiency of CIS leads to the differentiation of monocytes into immunosuppressive M2-like macrophages, promoting allergic inflammation.
CELLULAR & MOLECULAR IMMUNOLOGY
(2023)
Article
Oncology
Fernando Souza-Fonseca-Guimaraes, Gustavo R. Rossi, Laura F. Dagley, Momeneh Foroutan, Timothy R. McCulloch, Jumana Yousef, Hae-Young Park, Jennifer H. Gunter, Paul A. Beavis, Cheng-Yu Lin, Soroor Hediyeh-Zadeh, Tania Camilleri, Melissa J. Davis, Nicholas D. Huntington
CANCER IMMUNOLOGY RESEARCH
(2022)