Review
Biochemistry & Molecular Biology
Andrea Corsi, Cristina Bombieri, Maria Teresa Valenti, Maria Grazia Romanelli
Summary: Tau microtubule-associated proteins play important roles in neurons and are associated with several neurodegenerative diseases. Recent studies have focused on understanding the regulation of Tau splicing to develop new treatment approaches.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Review
Biochemistry & Molecular Biology
Luiza Steffens Reinhardt, Kira Groen, Cheryl Newton, Kelly A. Avery-Kiejda
Summary: The tumor suppressor protein p53 is activated in response to DNA damage and regulates the expression of genes involved in the DNA damage response. Different isoforms of p53 have been found to alter gene transcription or protein interactions, revealing an alternative DNA damage response. This review focuses on the role of p53 isoforms in the response to DNA damage. DNA damage-induced alternative splicing may modulate the expression of C-terminally truncated isoforms, while alternative translation plays a role in modulating the expression of N-terminally truncated isoforms. The DNA damage response induced by p53 isoforms may enhance the canonical p53 response or block cell death mechanisms, potentially contributing to chemoresistance in cancer. A better understanding of the involvement of p53 isoforms in cell fate decisions could reveal potential therapeutic targets in cancer and other diseases.
BIOCHIMICA ET BIOPHYSICA ACTA-REVIEWS ON CANCER
(2023)
Article
Biochemistry & Molecular Biology
So Mee Kwon, Seongki Min, Un-woo Jeoun, Min Seok Sim, Gu Hyun Jung, Sun Mi Hong, Byul A. Jee, Hyun Goo Woo, Changhan Lee, Gyesoon Yoon
Summary: Cellular senescence is a permanent growth arrest state that can lead to aging. Splicing perturbation can induce senescence, with Sp1 identified as a key regulator in the process. Changes in spliceosomal gene composition can serve as an early marker for senescence.
Article
Reproductive Biology
Xiaohong Yao, Chaofan Wang, Longjie Sun, Lu Yan, Xuexue Chen, Zheng Lv, Xiaomei Xie, Shuang Tian, Wenbo Liu, Lei Li, Hua Zhang, Jiali Liu
Summary: In this study, it was discovered that BCAS2 protein regulates pre-mRNA splicing in granulosa cells, affecting their proliferation and survival. BCAS2 participates in the PRP19 complex to mediate alternative splicing of E2f3 and Flt3l mRNA, thereby inhibiting the cell cycle. These findings reveal the function of BCAS2 in granulosa cells.
JOURNAL OF OVARIAN RESEARCH
(2023)
Article
Oncology
Venturina Stagni, Silvia Orecchia, Luca Mignini, Sara Beji, Ambra Antonioni, Cinzia Caggiano, Daniela Barila, Pamela Bielli, Claudio Sette
Summary: The interaction between the DNA damage response pathway and RNA metabolism is important in cancer. This study reveals that ATM kinase can phosphorylate RNA binding protein Sam68, regulating its function in the response to DNA damage. The findings uncover a new interaction between ATM and Sam68, providing insights into the functional interaction between the DDR pathway and RNA binding proteins.
Article
Dentistry, Oral Surgery & Medicine
Tiancheng Li, Han Wang, Yukun Jiang, Shuo Chen, Danyuan Huang, Zuping Wu, Xing Yin, Chenchen Zhou, Yuyu Li, Shujuan Zou
Summary: This study investigates the role of long noncoding RNAs (lncRNAs) in mediating the anabolic effects of intermittent parathyroid hormone (PTH) and contributing to cementum repair in orthodontically induced tooth root resorption (OIRR). The results reveal that intermittent PTH regulates cell proliferation and mineralization by modulating the Wnt pathway. The lncRNA LITTIP is identified as a key regulator of cementogenesis and it negatively regulates cementogenesis by promoting the expression of leucine-rich repeat-containing G-protein coupled receptor 6 (LGR6) through the RNA-binding protein heterogeneous nuclear ribonucleoprotein K (HnRNPK).
INTERNATIONAL JOURNAL OF ORAL SCIENCE
(2023)
Article
Biology
Tao Shen, Wangxiao Xia, Sainan Min, Zixuan Yang, Lehua Cheng, Wei Wang, Qianxi Zhan, Fanghong Shao, Xuehan Zhang, Zhiyu Wang, Yan Zhang, Guodong Shen, Huafeng Zhang, Li-Ling Wu, Guang-Yan Yu, Qing-Peng Kong, Xiangting Wang
Summary: This study identified a lncRNA gene related to Chr3q29 in tongue squamous carcinoma and demonstrated how its two variants, 887S and 887L, play opposing roles in tumor progression through the common target CA9. The mechanisms involve the activation of CA9 transcription by 887L through recruiting HIF1 alpha, while 887S suppresses CA9 through DNMT1-mediated DNA methylation. The findings highlight the fine control of hypoxia adaptation through CA9 by these two antagonistic lncRNA variants.
Article
Genetics & Heredity
Dongbo Ding, Xulun Sun, Matthew Y. H. Pang, Liwei An, Michael S. Y. Huen, Taobo Hu, Toyotaka Ishibashi
Summary: RecQL5 has two alternative splicing isoforms, with RECQL5 beta mainly functioning as a transcription repressor, while the newly discovered RECQL5 beta 1 has a specialized role in DNA damage response.
Article
Biochemistry & Molecular Biology
Jin Cai, Ningchao Wang, Guanglan Lin, Haowei Zhang, Weidong Xie, Yaou Zhang, Naihan Xu
Summary: RNA-binding protein MBNL2 plays a crucial role in regulating tumor cell proliferation and DNA damage response by modulating the PI3K/AKT pathway and affecting the expression of p21. Depletion of MBNL2 leads to increased phosphorylation levels of Chk1 and influences DNA damage response, ultimately altering tumor cell fate by inhibiting DNA damage repair and promoting DNA damage-induced apoptosis.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Biochemistry & Molecular Biology
Nareg Pinarbasi-Degirmenci, Ilknur Sur-Erdem, Vuslat Akcay, Yasemin Bolukbasi, Ugur Selek, Ihsan Solaroglu, Tugba Bagci-Onder
Summary: By applying fractionated radiotherapy over a long time and selecting irradiation-survivor glioblastoma cells, clinically relevant irradiation-exposed models were generated. The cells exhibited slower growth, resistance to secondary irradiation, upregulation of DDR-related genes, and better DNA repair capacity. The utility of combining DDR inhibitors and irradiation was demonstrated for both naive and IR-Surv glioblastoma cells, as long as cells are refrained from hypoxic conditions.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Editorial Material
Biochemistry & Molecular Biology
William G. Dunphy
Summary: Frattini et al. (2021) demonstrate that TopBP1 forms phase-separated nuclear condensates to promote activation of ATR in cells experiencing genomic stress.
Article
Oncology
Alexander C. Leeksma, Ingrid A. M. Derks, M. Haidar Kasem, Emine Kilic, Annelies de Klein, Martine J. Jager, Arjan A. van de Loosdrecht, Joop H. Jansen, Veronika Navrkalova, Laura M. Faber, Nadja Zaborsky, Alexander Egle, Thorsten Zenz, Sarka Pospisilova, Omar Abdel-Wahab, Arnon P. Kater, Eric Eldering
Summary: Recurrent mutations in SF3B1 are linked to various malignancies and may impact biological effects through altered signaling pathways, but show no significant effects on ATM/p53 response, H2AX phosphorylation, and sensitivity to fludarabine in treatment-naive CLL. Cryptic transcripts associated with SF3B1 mutations are degraded via NMD, with increased expression observed after NMD inhibition. Further research may explore the potential benefit of NMD modulatory agents in SF3B1-mutant patients.
FRONTIERS IN ONCOLOGY
(2021)
Article
Plant Sciences
Yunqing Jian, Xia Chen, Kewei Sun, Zunyong Liu, Danni Cheng, Jie Cao, Jianzhao Liu, Xiaofei Cheng, Liang Wu, Feng Zhang, Yuming Luo, Matthias Hahn, Zhonghua Ma, Yanni Yin
Summary: This study reveals a novel function of SUMOylation in DNA damage response (DDR) and virulence in Fusarium graminearum, a causal agent of Fusarium head blight of cereal crops. It demonstrates that the transcription factor FgSR is SUMOylated upon DNA damage stress, which regulates its nuclear-cytoplasmic partitioning, phosphorylation, and interaction with chromatin remodeling complex SWI/SNF to activate the expression of DDR-related genes. Moreover, the SWI/SNF complex recruits splicing-related NineTeen Complex to modulate pre-mRNA splicing during DDR. These findings advance the understanding of the delicate regulation of DDR by SUMOylation in pathogenic fungi, and extend the knowledge of cooperation of SUMOylation and pre-mRNA splicing in DDR in eukaryotes.
Article
Cardiac & Cardiovascular Systems
Yuanbiao Zhao, Andrew S. Riching, Walter E. Knight, Congwu Chi, Lindsey J. Broadwell, Yanmei Du, Mostafa Abdel-Hafiz, Amrut Ambardekar, David C. Irwin, Catherine Proenza, Hongyan Xu, Leslie A. Leinwand, Lori A. Walker, Kathleen C. Woulfe, Michael R. Bristow, Peter M. Buttrick, Kunhua Song
Summary: This study reveals that a long noncoding RNA, Trdn-as, regulates cardiac function and triadin levels in the heart by controlling alternative splicing of the triadin gene. Knockout of Trdn-as in mice leads to downregulation of cardiac triadin, impaired Ca2+ handling, and premature death. Furthermore, Trdn-as plays an essential role in recruiting splicing factors to triadin precursor mRNA. These findings suggest potential therapeutics for heart disease by targeting the long noncoding RNA or pathways regulating alternative splicing.
Article
Oncology
Guosheng Lyu, Peng Sue, Xiaohe Hao, Shiming Chen, Shuai Ren, Zixiao Zhao, Yaoqin Gong, Qiao Liu, Changshun Shao
Summary: RECQL4 is highly expressed in ESCC and is associated with poor differentiation, enhanced invasion, and metastasis. It promotes cell proliferation and migration, regulates DNA damage, redox homeostasis, and cell survival.
CANCER BIOLOGY & MEDICINE
(2021)
Article
Oncology
Jorge Barriuso, Raghavendar T. Nagaraju, Shreya Belgamwar, Bipasha Chakrabarty, George J. Burghel, Helene Schlecht, Lucy Foster, Elaine Kilgour, Andrew J. Wallace, Michael Braun, Caroline Dive, D. Gareth Evans, Robert G. Bristow, Mark P. Saunders, Sarah T. O'Dwyer, Omer Aziz
Summary: The study identified gene dysregulation in peritoneal metastasis that enhances tumor resistance and inflammatory changes. After adjusting for age, gender, and stage, the gene signature showed significant prognostic value for both overall survival and disease-free survival.
CLINICAL CANCER RESEARCH
(2021)
Article
Cell Biology
Danish Memon, Michael B. Gill, Evangelia K. Papachristou, David Ochoa, Clive S. D'Santos, Martin L. Miller, Pedro Beltrao
Summary: The study integrated genomic and proteomic data from thousands of tumor samples to identify CNVs that play a key role in cancer by altering cell signaling states. Known kinase-substrate relationships were recapitulated, and potential causal genes were prioritized through network analysis. The research also showed evidence of kinase addiction in cancer cell lines and proposed the copy number status of genes as a useful predictor for impacting kinase inhibition in anticancer therapies.
Editorial Material
Medicine, Research & Experimental
Danish Memon, Inigo Barrio-Hernandez, Pedro Beltrao
Summary: The COVID-19 pandemic has spurred an unprecedented surge in global scientific and medical research efforts. A recent study analyzed proteomes from COVID-19 patients, providing a comprehensive characterization of plasma proteome changes during infection.
EMBO MOLECULAR MEDICINE
(2021)
Meeting Abstract
Oncology
Rebecca Lee, Oskar Wysocki, Cong Zhou, Antonio Calles, Leonie Eastlake, Sarju Ganatra, Michelle Harrison, Laura Horsley, Prerana Huddar, Khurum Khan, Hayley Mckenzie, Carlo Palmieri, Jacobo Rogado Revuelta, Anne Thomas, Caroline Wilson, Tim Cooksley, Caroline Dive, Andre Freitas, Anne Caroline Armstrong
JOURNAL OF CLINICAL ONCOLOGY
(2021)
Review
Oncology
Melissa Frizziero, Elaine Kilgour, Kathryn L. Simpson, Dominic G. Rothwell, David A. Moore, Kristopher K. Frese, Melanie Galvin, Angela Lamarca, Richard A. Hubner, Juan W. Valle, Mairead G. McNamara, Caroline Dive
Summary: Poorly differentiated neuroendocrine carcinomas (PD-NEC) are rare cancers that have gained attention due to improved diagnostic methods and the phenomenon of NE lineage plasticity. However, effective treatment options for PD-NEC patients are challenging due to the lack of targetable molecular drivers, limited preclinical models, and validated biomarkers.
CLINICAL CANCER RESEARCH
(2022)
Article
Multidisciplinary Sciences
Lucy G. Thorne, Mehdi Bouhaddou, Ann-Kathrin Reuschl, Lorena Zuliani-Alvarez, Ben Polacco, Adrian Pelin, Jyoti Batra, Matthew V. X. Whelan, Myra Hosmillo, Andrea Fossati, Roberta Ragazzini, Irwin Jungreis, Manisha Ummadi, Ajda Rojc, Jane Turner, Marie L. Bischof, Kirsten Obernier, Hannes Braberg, Margaret Soucheray, Alicia Richards, Kuei-Ho Chen, Bhavya Harjai, Danish Memon, Joseph Hiatt, Romel Rosales, Briana L. McGovern, Aminu Jahun, Jacqueline M. Fabius, Kris White, Ian G. Goodfellow, Yasu Takeuchi, Paola Bonfanti, Kevan Shokat, Natalia Jura, Klim Verba, Mahdad Noursadeghi, Pedro Beltrao, Manolis Kellis, Danielle L. Swaney, Adolfo Garcia-Sastre, Clare Jolly, Greg J. Towers, Nevan J. Krogan
Summary: The Alpha variant of SARS-CoV-2 effectively suppresses innate immune responses in airway epithelial cells compared to first-wave isolates, possibly due to increased expression of specific viral antagonist proteins. This enhanced innate immune suppression may increase the likelihood of successful transmission of the Alpha variant and potentially impact in vivo replication and infection duration. Mutations outside the spike coding region, such as those observed in the N and Orf9b regulatory regions, play a crucial role in the adaptation of SARS-CoV-2 variants to humans.
Article
Biotechnology & Applied Microbiology
Cristina Vieitez, Bede P. Busby, David Ochoa, Andre Mateus, Danish Memon, Marco Galardini, Umut Yildiz, Matteo Trovato, Areeb Jawed, Alexander G. Geiger, Michaela Oborska-Oplova, Clement M. Potel, Sibylle C. Vonesch, Chelsea Szu Tu, Mohammed Shahraz, Frank Stein, Lars M. Steinmetz, Vikram G. Panse, Kyung-Min Noh, Mikhail M. Savitski, Athanasios Typas, Pedro Beltrao
Summary: Phosphorylation plays a critical role in regulating various cellular processes, but functional annotations for the majority of discovered phosphosites are lacking. A chemical genetic approach was used to study the functional relevance of phosphosites in yeast, revealing potential functional significance for 42% of the sites. This high-throughput method allows for the functional characterization of individual phosphosites at scale.
NATURE BIOTECHNOLOGY
(2022)
Article
Cell Biology
Aishwarya Payapilly, Ryan Guilbert, Tine Descamps, Gavin White, Peter Magee, Cong Zhou, Alastair Kerr, Kathryn L. Simpson, Fiona Blackhall, Caroline Dive, Angeliki Malliri
Summary: The study shows that the TIAM1-RAC1 signaling pathway promotes survival of SCLC cells through nuclear sequestration of Nur77.
Article
Oncology
C. Zhou, J. O'Connor, A. Backen, J. W. Valle, J. Bridgewater, C. Dive, G. C. Jayson
Summary: In this study, it was found that plasma Tie2 (pTie2) can serve as a response biomarker for vascular endothelial growth factor inhibitors (VEGFi) treatment, predicting treatment response and disease progression. By integrating data from different types of cancer, it was demonstrated that pTie2 can guide the optimal use of VEGFi in clinical practice.
Article
Oncology
Lois Gardner, Kostas Kostarelo, Parag Mallick, Caroline Dive, Marilena Hadjidemetriou
Summary: Liquid biopsy assays offer opportunities for early detection of cancer and improved management of the disease by detecting cancer-associated molecular alterations in blood. This Perspective reviews key advances in liquid biopsy-based multi-omics approaches for biomarker discovery and introduces the 'nano-omics' paradigm, which utilizes nanotechnology tools for the analysis of blood-circulating cancerome.
NATURE REVIEWS CLINICAL ONCOLOGY
(2022)
Review
Oncology
Ann Tivey, Matt Church, Dominic Rothwell, Caroline Dive, Natalie Cook
Summary: Over the past decade, liquid biopsy techniques have emerged as alternatives to traditional tissue biopsy samples. Majority of research in this field has focused on blood-based biomarkers, especially circulating tumor DNA (ctDNA) derived from plasma. However, ctDNA can also be obtained from non-blood sources such as urine, cerebrospinal fluid, and pleural or peritoneal fluid. In this review, the authors discuss the advances in analyzing ctDNA from non-blood sources, exploring the distinct advantages and technical aspects of non-blood ctDNA assay development. They also reflect on when non-blood ctDNA can have advantages over plasma ctDNA and the challenges of translating these assays into clinical use.
NATURE REVIEWS CLINICAL ONCOLOGY
(2022)
Article
Oncology
Oskar Wysocki, Cong Zhou, Jacobo Rogado, Prerana Huddar, Rohan Shotton, Ann Tivey, Laurence Albiges, Angelos Angelakas, Dirk Arnold, Theingi Aung, Kathryn Banfill, Mark Baxter, Fabrice Barlesi, Arnaud Bayle, Benjamin Besse, Talvinder Bhogal, Hayley Boyce, Fiona Britton, Antonio Calles, Luis Castelo-Branco, Ellen Copson, Adina Croitoru, Sourbha S. Dani, Elena Dickens, Leonie Eastlake, Paul Fitzpatrick, Stephanie Foulon, Henrik Frederiksen, Sarju Ganatra, Spyridon Gennatas, Andreas Glenthoj, Fabio Gomes, Donna M. Graham, Christina Hague, Kevin Harrington, Michelle Harrison, Laura Horsley, Richard Hoskins, Zoe Hudson, Lasse H. Jakobsen, Nalinie Joharatnam-Hogan, Sam Khan, Umair T. Khan, Khurum Khan, Alexandra Lewis, Christophe Massard, Alec Maynard, Hayley McKenzie, Olivier Michielin, Anne C. Mosenthal, Berta Obispo, Carlo Palmieri, Rushin Patel, George Pentheroudakis, Solange Peters, Kimberly Rieger-Christ, Timothy Robinson, Emanuela Romano, Michael Rowe, Marina Sekacheva, Roseleen Sheehan, Alexander Stockdale, Anne Thomas, Lance Turtle, David Vinal, Jamie Weaver, Sophie Williams, Caroline Wilson, Caroline Dive, Donal Landers, Timothy Cooksley, Andre Freitas, Anne C. Armstrong, Rebecca J. Lee
Summary: Indicators of COVID-19 severity in cancer patients remain predictive across different waves of the pandemic. Vaccination and steroid use have contributed to improved outcomes. The CORONET model performs well regardless of SARS-CoV-2 variants.
Meeting Abstract
Oncology
N. C. Ramchander, N. Billy Graham Mariam, S. Rack, K. Shohdy, A. Ortega Franco, F. Thistlethwaite, D. M. Graham, L. Carter, S. Dransfield, A. Henshaw, E. Darlington, D. Rothwell, G. J. Burghel, C. Dive, M. G. Krebs, N. Cook
ANNALS OF ONCOLOGY
(2022)
Article
Biochemistry & Molecular Biology
David F. Burke, Patrick Bryant, Inigo Barrio-Hernandez, Danish Memon, Gabriele Pozzati, Aditi Shenoy, Wensi Zhu, Alistair S. Dunham, Pascal Albanese, Andrew Keller, Richard A. Scheltema, James E. Bruce, Alexander Leitner, Petras Kundrotas, Pedro Beltrao, Arne Elofsson
Summary: In this study, the authors investigate the use of AlphaFold2 to predict protein structures in the human protein-protein interactome and discuss its limitations. They demonstrate the high confidence of the predicted models and identify potential mechanisms for disease mutations. Additionally, they show the application of predicted binary complexes in expanding our understanding of human cell biology.
NATURE STRUCTURAL & MOLECULAR BIOLOGY
(2023)
Meeting Abstract
Oncology
George J. Fromm, Danish Memon, Suresh de Silva, Kyung Jin Yoo, Kellsey Johannes, Casey Shuptrine, Jaya Miriyala, Arpita Patel, Fatima Rangwala, Zachary Opheim, Thuy-Ai Nguyen, Louis Gonzalez, Fatima Rangwala, Taylor H. Schreiber, Matthew D. Hellmann, Martin L. Miller, Taylor H. Schreiber