Article
Biochemistry & Molecular Biology
Meng-Xi Wang, Li Yan, Juan Chen, Jun-Mei Zhao, Jiang Zhu, Shan-He Yu
Summary: This study explored the feasibility of reducing the malignant characteristics of t(8;21) AML cells by reinforcing their endogenous differentiation potential. The results showed that in an AE9a murine model, the process of erythroid differentiation was accompanied by a decline or loss of leukemia-initiating potential. Therefore, enhancing the erythroid differentiation of t(8;21) AML cells may be a promising intervention strategy.
Article
Biochemistry & Molecular Biology
Yoshiro Hirasaki, Atsushi Okabe, Masaki Fukuyo, Bahityar Rahmutulla, Yasunobu Mano, Motoaki Seki, Takayuki Hoshii, Takao Namiki, Atsushi Kaneda
Summary: This study found that cinobufagin can induce apoptosis in human acute myeloid leukaemia cells and has inhibitory effects on c-Myc. Transcriptomic analysis and gene set enrichment analysis further revealed its mechanisms of action.
CHEMICO-BIOLOGICAL INTERACTIONS
(2022)
Article
Hematology
Maria-Riera Pique-Borras, Zivojin Jevtic, Frederik Otzen Bagger, Jonathan Seguin, Rathick Sivalingam, Matheus Filgueira Bezerra, Amber Louwagie, Sabine Juge, Ioannis Nellas, Robert Ivanek, Alexandar Tzankov, Ute M. Moll, Oriano Cantillo, Ramona Schulz-Heddergott, Alexandre Fagnan, Thomas Mercher, Juerg Schwaller
Summary: The NFIA-ETO2 fusion is a chromosomal translocation found exclusively in pediatric patients with pure erythroid leukemia (PEL). The fusion protein impairs erythroid differentiation and promotes proliferation in murine erythroblasts and fetal liver-derived erythroblasts. However, it does not induce disease upon transplantation into mice. In the presence of TP53(R248Q) mutation, NFIA-ETO2 acquires clonogenic activity and induces a transplantable PEL-like disease. Molecular studies reveal that NFIA-ETO2 represses erythroid differentiation by targeting genes with NFI binding sites and ETO2 modifications, while TP53(R248Q) enhances self-renewal and survival potential.
Article
Endocrinology & Metabolism
Jie Zhang, Peilang Yang, Dan Liu, Min Gao, Jizhuang Wang, Xiqiao Wang, Yan Liu, Xiong Zhang
Summary: Dysfunction in keratinocyte differentiation in diabetic skin is closely related to the overexpression of c-Myc and S100A6, with potential mechanisms including activation of the WNT/beta-catenin pathway and direct regulation of S100A6 expression. These findings suggest that c-Myc and S100A6 may be potential targets for the treatment of chronic diabetic wounds.
FRONTIERS IN ENDOCRINOLOGY
(2021)
Article
Cell Biology
Mohammad Houshmand, Nicoletta Vitale, Francesca Orso, Alessandro Cignetti, Ivan Molineris, Valentina Gaidano, Stefano Sainas, Marta Giorgis, Donatella Boschi, Carmen Fava, Alice Passoni, Marta Gai, Massimo Geuna, Federica Sora, Alessandra Iurlo, Elisabetta Abruzzese, Massimo Breccia, Olga Mulas, Giovanni Caocci, Fausto Castagnetti, Daniela Taverna, Salvatore Oliviero, Fabrizio Pane, Marco Lucio Lolli, Paola Circosta, Giuseppe Saglio
Summary: The study shows that the newly developed DHODH inhibitor, Meds433, is highly effective in targeting CML cells by activating the apoptotic pathway and inducing metabolic stress. This finding suggests that DHODH inhibition is a promising approach for targeting CML stem/progenitor cells.
CELL DEATH & DISEASE
(2022)
Article
Cell Biology
Marc Garcia-Montolio, Cecilia Ballare, Enrique Blanco, Arantxa Gutierrez, Sergi Aranda, Antonio Gomez, Chung H. Kok, David T. Yeung, Timothy P. Hughes, Pedro Vizan, Luciano Di Croce
Summary: Polycomb group proteins, including PHF19, play important roles in regulating cell fate determination and could be potential therapeutic targets for myeloid leukemia treatment. PHF19 depletion reduces cell proliferation and promotes leukemia cell differentiation, with its homolog MTF2 partially compensating for its effects in specific gene targets.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2021)
Article
Cell Biology
Tingting Cui, Jiaxin Huang, Yingning Sun, Bolin Ning, Fang Mu, Xin You, Yaqi Guo, Hui Li, Ning Wang
Summary: KLF2 inhibits chicken preadipocyte differentiation at least in part through direct downregulation of PPAR gamma 1 expression. This mechanism involves KLF2 regulation of the P1 promoter of the PPAR gamma gene and effects on histone modifications.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2021)
Article
Pharmacology & Pharmacy
Xinye Yao, Yanbo Xue, Qiang Ma, Yajun Bai, Pu Jia, Yiman Zhang, Baochang Lai, Shuting He, Qiong Ma, Junbo Zhang, Hongyan Tian, Qian Yin, Xiaohui Zheng, Xiaopu Zheng
Summary: 221S-1a, a novel synthetic compound, has antiangiogenic properties by blocking the ERK1/2/c-Myc pathway, thus reducing tumor and OIR retinal angiogenesis.
EUROPEAN JOURNAL OF PHARMACOLOGY
(2023)
Article
Cell Biology
Xiaoling Zhang, Xianling Cong, Xiangting Jin, Yu'e Liu, Tong Zhang, Xinyuan Fan, Xiyao Shi, Xiaoying Zhang, Xue Wang, Yong-Guang Yang, Xiangpeng Dai
Summary: The transcription factor MYCN is frequently amplified and overexpressed in various cancers, and is considered undruggable. In this study, BRCA1-associated protein-1 (BAP1) is identified as an upstream regulator that stabilizes MYCN through direct binding. Depletion of BAP1 inhibits neuroblastoma tumor cell growth and migration, and confers cellular resistance to BET protein inhibitor JQ1 and Aurora A kinase inhibitor Alisertib. Our findings suggest that BAP1 could be a potential therapeutic target for MYCN-amplified neuroblastoma.
CELL DEATH & DISEASE
(2023)
Article
Biotechnology & Applied Microbiology
Lana Vukadin, Jung-Hyun Kim, Eun Young Park, Joshua K. Stone, Nathan Ungerleider, Melody C. Baddoo, Hyun Kyung Kong, Alexander Richard, Johnny Tran, Hannah Giannini, Erik K. Flemington, Ssang-Taek Steve Lim, Eun-Young Erin Ahn
Summary: This study reveals that the chromosome 21-encoded protein SON inhibits megakaryocytic differentiation by suppressing RUNX1 and megakaryocytic gene expression. Overexpression of SON in AMKL cells leads to impaired differentiation, while knockdown of SON induces the onset of megakaryocytic differentiation.
CANCER GENE THERAPY
(2021)
Article
Oncology
Mengping Xi, Shanshan Guo, Caicike Bayin, Lijun Peng, Florent Chuffart, Ekaterina Bourova-Flin, Sophie Rousseaux, Saadi Khochbin, Jian-Qing Mi, Jin Wang
Summary: This study found that the HDAC inhibitor chidamide has an anti-tumor effect on T-ALL cells, particularly by inhibiting the NOTCH1-MYC signaling axis. Clinical trial results support that chidamide treatment reduces minimal residual disease in patients and is well tolerated.
FRONTIERS OF MEDICINE
(2022)
Article
Dentistry, Oral Surgery & Medicine
Chen Zhang, Weilong Ye, Mengyao Zhao, Lujue Long, Dengsheng Xia, Zhipeng Fan
Summary: This study investigated the role and mechanism of MLL1 in the neurogenesis of SCAPs. The results showed that MLL1 interacts with WDR5 and represses HES1, thereby inhibiting the neurogenic potential of SCAPs. These findings provide a potential therapeutic target for promoting the recovery of motor function in SCI patients.
INTERNATIONAL JOURNAL OF ORAL SCIENCE
(2023)
Article
Hematology
Jason R. Marcero, James E. Cox, Hector A. Bergonia, Amy E. Medlock, John D. Phillips, Harry A. Dailey
Summary: Itaconate, produced by macrophages during inflammatory response, inhibits hemoglobin synthesis in red blood cells and may lead to anemia. It acts by blocking tetrapyrrole synthesis pathway and causing alterations in cellular metabolite pools.
Article
Biotechnology & Applied Microbiology
Wen Liu, Fanjun Cheng
Summary: Studies have shown that circCRKL plays a role in inhibiting cell proliferation in AML by sponging miR-196a-5p and miR-196b-5p to promote p27 expression. This suggests circCRKL as a potential new target for AML therapy.
Article
Biotechnology & Applied Microbiology
Yu-Hsuan Fu, Da-Liang Ou, Yi-Ru Yang, Kuan-Wei Su, Chien-Yuan Chen, Hwei-Fan Tien, Zheng-Sheng Lai, Che-Kun James Shen, Hsiung-Fei Chien, Liang-In Lin
Summary: Cabozantinib promotes erythroid differentiation in leukemia cells through upregulating heme biosynthesis, hemoglobin production, and erythroid-associated pathways, while inhibiting cell proliferation by downregulating cell survival pathways.
CANCER GENE THERAPY
(2022)
Article
Oncology
Judit Liano-Pons, M. Carmen Lafita-Navarro, Lorena Garcia-Gaipo, Carlota Colomer, Javier Rodriguez, Alex von Kriegsheim, Peter J. Hurlin, Fabiana Ourique, M. Dolores Delgado, Anna Bigas, M. Lluis Espinosa, Javier Leon
Summary: The study finds that MNT acts as a transcription factor to repress the activation of the NF-kappa B pathway by interacting with REL, and forms a complex with REL to inhibit the expression of REL target genes through two mechanisms.
Article
Oncology
Nicholas T. Younger, Mollie L. Wilson, Anabel Martinez Lyons, Edward J. Jarman, Alison M. Meynert, Graeme R. Grimes, Konstantinos Gournopanos, Scott H. Waddell, Peter A. Tennant, David H. Wilson, Rachel Guest, Stephen J. Wigmore, Juan Carlos Acosta, Timothy J. Kendall, Martin S. Taylor, Duncan Sproul, Pleasantine Mill, Luke Boulter
Summary: This study investigated the role of genetic heterogeneity in driving intrahepatic cholangiocarcinoma (ICC) and identified novel tumor suppressors that interact with the RAS oncoprotein to promote ICC growth.
Article
Biochemistry & Molecular Biology
Irene Fernandez-Duran, Andrea Quintanilla, Nuria Tarrats, Jodie Birch, Priya Hari, Fraser R. Millar, Anthony B. Lagnado, Vanessa Smer-Barreto, Morwenna Muir, Valerie G. Brunton, Joao F. Passos, Juan Carlos Acosta
Summary: In this study, it was revealed that caspase-4 plays a critical role in cellular senescence, dependent on gasdermin-D and tumor suppressor p53. This pathway is conserved in the cellular response to oncogenic stress.
CELL DEATH AND DIFFERENTIATION
(2022)
Article
Cell Biology
Nuria Ferrandiz, Laura Downie, Georgina P. Starling, Stephen J. Royle
Summary: Misalignment of chromosomes during mitosis can result in chromosome missegregation and the formation of micronuclei, which are associated with cancer. A study showed that chromosomes located beyond the exclusion zone become ensheathed in multiple layers of endomembranes, leading to delayed mitosis and increased frequency of chromosome missegregation and micronucleus formation. Clearance of endomembranes can rescue those chromosomes that were destined for missegregation, indicating that endomembranes promote the missegregation of misaligned chromosomes outside the exclusion zone and pose a risk factor for aneuploidy.
JOURNAL OF CELL BIOLOGY
(2022)
Article
Multidisciplinary Sciences
Joy Edwards-Hicks, Huizhong Su, Maurizio Mangolini, Kubra K. Yoneten, Jimi Wills, Giovanny Rodriguez-Blanco, Christine Young, Kevin Cho, Heather Barker, Morwenna Muir, Ania Naila Guerrieri, Xue-Feng Li, Rachel White, Piotr Manasterski, Elena Mandrou, Karen Wills, Jingyu Chen, Emily Abraham, Kianoosh Sateri, Bin-Zhi Qian, Peter Bankhead, Mark Arends, Noor Gammoh, Alex von Kriegsheim, Gary J. Patti, Andrew H. Sims, Juan Carlos Acosta, Valerie Brunton, Kamil R. Kranc, Maria Christophorou, Erika L. Pearce, Ingo Ringshausen, Andrew J. Finch
Summary: MYC activation enhances global transcription and translation, creating a metabolic demand. Glutamine limitation leads to an imbalance of metabolic supply and demand, sensitising cells to apoptosis. Glutamine supports the viability of MYC-overexpressing cells through TCA cycle energetics rather than biosynthetic mechanism.
NATURE COMMUNICATIONS
(2022)
Article
Biochemistry & Molecular Biology
Laura I. Lascarez-Lagunas, Saravanapriah Nadarajan, Marina Martinez-Garcia, Julianna N. Quinn, Elena Todisco, Tanuj Thakkar, Elizaveta Berson, Don Eaford, Oliver Crawley, Alex Montoya, Peter Faull, Nuria Ferrandiz, Consuelo Barroso, Sara Labella, Emily Koury, Sarit Smolikove, Monique Zetka, Enrique Martinez-Perez, Monica P. Colaiacovo
Summary: The choice of DSB repair pathway during meiosis is still unknown. In C. elegans, DSB repair occurs within the SC structure formed between homologous chromosomes. This study demonstrates that SYP-4, a component of the SC, is phosphorylated in response to DSBs and the ATM/ATR DNA damage response kinases. This phosphorylation plays a critical role in maintaining the structural integrity of the SC following DSB formation and promoting normal DSB repair progression and crossover patterning.
Article
Biochemistry & Molecular Biology
Alejandro P. Ugalde, Gabriel Bretones, David Rodriguez, Victor Quesada, Francisco Llorente, Raul Fernandez-Delgado, Miguel Angel Jimenez-Clavero, Jesus Vazquez, Enrique Calvo, Isaac Tamargo-Gomez, Guillermo Marino, David Roiz-Valle, Daniel Maeso, Miguel Araujo-Voces, Yaiza Espanol, Carles Barcelo, Jose Mp Freije, Alejandro Lopez-Soto, Carlos Lopez-Otin
Summary: A genome-wide CRISPR/Cas9-based screen in SARS-CoV-2-infected lung cancer cells identified two critical host factors, SPNS1 and PLAC8, that affect viral entry. These findings provide a better understanding of the virus-host interactions.
Article
Multidisciplinary Sciences
Maria Pascual-Torner, Dido Carrero, Jose G. Perez-Silva, Diana Alvarez-Puente, David Roiz-Valle, Gabriel Bretones, David Rodriguez, Daniel Maeso, Elena Mateo-Gonzalez, Yaiza Espanol, Guillermo Marino, Jose Luis Acuna, Victor Quesada, Carlos Lopez-Otin
Summary: Research has found that Turritopsis dohrnii has the ability to regenerate, and this ability is associated with variations and expansions of several genes related to replication, DNA repair, telomere maintenance, stem cell population, and intercellular communication. Furthermore, during its life cycle reversal process, silencing of polycomb repressive complex 2 targets and activation of pluripotency targets are proposed to be key factors in T. dohrnii's ability to undergo rejuvenation.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Article
Cell Biology
Diana Campos-Iglesias, Julia M. Fraile, Gabriel Bretones, Alejandro A. Montero, Elena Bonzon-Kulichenko, Jesus Vazquez, Carlos Lopez-Otin, Jose M. P. Freije
Summary: USP49 deubiquitinase is identified as a novel regulator of the spindle checkpoint. Loss of USP49 impairs proliferation and increases aneuploidy in cancer cell lines. USP49-depleted cells can overcome SAC-induced arrest in presence of nocodazole.
CELL DEATH & DISEASE
(2023)
Article
Cell Biology
Me'ghane Sittewelle, Nuria Ferrandiz, Mary Fesenko, Stephen J. Royle
Summary: The biology of a cell is composed of dynamic processes, controlled by various proteins and molecules. Microscopy plays a crucial role in understanding these processes at a molecular level. Genetically encoded imaging tools, categorized into observation, inhibition, and activation strategies, have been developed to study protein function in dynamic processes. This article provides examples and a guide on using these tools to dissect protein function in cellular processes, with a focus on rapid protein modification and observing resulting cell state changes, inspiring readers for future imaging experiments.
JOURNAL OF CELL SCIENCE
(2023)
Article
Multidisciplinary Sciences
Vanessa Smer-Barreto, Andrea Quintanilla, Richard J. R. Elliott, John C. Dawson, Jiugeng Sun, Victor M. Campa, Alvaro Lorente-Macias, Asier Unciti-Broceta, Neil O. Carragher, Juan Carlos Acosta, Diego A. Oyarzun
Summary: Cellular senescence is a stress response involved in aging and various diseases, and the discovery of new senolytics is limited. In this study, the authors used machine learning models trained on published data to identify three senolytic compounds, resulting in significant cost reduction in drug screening. These compounds have comparable potency to known senolytics, and one of them, oleandrin, shows improved potency compared to existing alternatives. This approach demonstrates the potential of artificial intelligence in utilizing heterogeneous drug screening data for early-stage drug discovery.
NATURE COMMUNICATIONS
(2023)
Article
Cell Biology
Isaac Tamargo-Gomez, Gemma G. Martinez-Garcia, Maria F. Suarez, Pablo Mayoral, Gabriel Bretones, Aurora Astudillo, Jesus Prieto-Lloret, Christina Sveen, Antonio Fueyo, Nikolai Engedal, Carlos Lopez-Otin, Guillermo Marino
Summary: The study of mutant mice deficient in Atg4c reveals the important role of Atg4c in tissue-specific autophagy and cellular immunity.
Article
Biochemistry & Molecular Biology
Ester Molina, Lucia Garcia-Gutierrez, Vanessa Junco, Mercedes Perez-Olivares, Virginia G. de Yebenes, Rosa Blanco, Laura Quevedo, Juan C. Acosta, Ana V. Marin, Daniela Ulgiati, Ramon Merino, M. Dolores Delgado, Ignacio Varela, Jose R. Regueiro, Ignacio Moreno de Alboran, Almudena R. Ramiro, Javier Leon
Summary: The researchers discovered that the oncogenic transcription factor MYC directly targets the EBV receptor CR2 gene, proposing an alternative hypothesis to the widely accepted mechanism of EBV infection.
Article
Biochemistry & Molecular Biology
Lorena Agudo-Ibanez, Marta Morante, Lucia Garcia-Gutierrez, Andrea Quintanilla, Javier Rodriguez, Alberto Munoz, Javier Leon, Piero Crespo
Summary: The transcription factor MYC is regulated by the kinase activity of ERK2 and plays a role in cell proliferation, transformation, and survival. ERK2 was found to directly regulate MYC transcription by binding to the MYC promoter. ERK2 increased MYC expression and protein abundance in the nucleus, independent of its kinase activity, through interactions with CDK9. These findings demonstrate a kinase-independent role for ERK2 in promoting MYC expression by anchoring CDK9 to the MYC promoter.
Article
Biology
Nuria Ferrandiz, Stephen J. Royle
Summary: This article outlines a method that combines light microscopy and 3D volume electron microscopy to visualize chromosomes and endomembranes in mitosis, allowing researchers to gain a more comprehensive understanding of the spindle function in the intracellular context.
