Article
Biochemistry & Molecular Biology
Jin Zhou, Jeremy M. Simon, Chengheng Liao, Cheng Zhang, Lianxin Hu, Giada Zurlo, Xijuan Liu, Cheng Fan, Austin Hepperla, Liwei Jia, Vanina Toffessi Tcheuyap, Hua Zhong, Roy Elias, Jin Ye, W. Mike Henne, Payal Kapur, Deepak Nijhawan, James Brugarolas, Qing Zhang
Summary: The JMJD6-DGAT1 axis plays a critical role in ccRCC tumor development. JMJD6 interacts with RBM39 and co-occupies the DGAT1 gene promoter to induce DGAT1 expression. Silencing JMJD6 reduces DGAT1 expression, leading to inhibition of lipid droplet formation and tumorigenesis. Pharmacological inhibition of DGAT1 suppresses lipid droplet formation and ccRCC tumorigenesis.
Article
Multidisciplinary Sciences
Matthew E. Cockman, Yoichiro Sugimoto, Hamish B. Pegg, Norma Masson, Eidarus Salah, Anthony Tumber, Helen R. Flynn, Joanna M. Kirkpatrick, Christopher J. Schofield, Peter J. Ratcliffe
Summary: JMJD6 is a 2-oxoglutarate-dependent dioxygenase involved in various cellular processes. Through mass spectrometry analysis, we identified 150 lysine hydroxylation sites on 48 protein substrates catalyzed by JMJD6, including 19 hydroxylation sites on BRD4. Most of these substrates are associated with membraneless organelle formation, suggesting a potential role for JMJD6 in regulating subcellular partitioning in response to stress.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Review
Biochemistry & Molecular Biology
Mengchao Yu, Jie Lun, Hongwei Zhang, Lei Zhu, Gang Zhang, Jing Fang
Summary: The hypoxia-inducible factor prolyl hydroxylases (PHDs) are enzymes that regulate the response to oxygen levels by hydroxylating prolyl residues of HIF alpha. Studies show they also have additional functions in protein stability, enzyme activity, and protein-protein interactions.
INTERNATIONAL JOURNAL OF BIOCHEMISTRY & CELL BIOLOGY
(2021)
Article
Medicine, Research & Experimental
Ting Guo, Chao Gu, Bin Li, Congjian Xu
Summary: The study revealed that PLODs are generally overexpressed in ovarian cancer, and each PLOD may not be functionally redundant. The association between PLOD3 and gap junctions warrants further investigation.
LABORATORY INVESTIGATION
(2021)
Review
Biochemistry & Molecular Biology
Claudia A. Staab-Weijnitz
Summary: Organ fibrosis is a disease characterized by epithelial injury and abnormal tissue repair, resulting in excessive deposition of collagen. It frequently leads to organ failure and is estimated to be responsible for one-third of global deaths. This review summarizes recent advances in targeting collagen biosynthesis, maturation, and degradation for the treatment of fibrotic diseases. The potential therapeutic targets and their specificity for collagen biology and disease-associated collagen are discussed, along with strategies for targeted drug delivery.
AMERICAN JOURNAL OF RESPIRATORY CELL AND MOLECULAR BIOLOGY
(2022)
Article
Multidisciplinary Sciences
Masahiko Terajima, Yuki Taga, Becky K. Brisson, Amy C. Durham, Kotaro Sato, Katsuhiro Uzawa, Tomoaki Saito, Shunji Hattori, Karin U. Sorenmo, Mitsuo Yamauchi, Susan W. Volk
Summary: The study characterized the molecular and morphological phenotypes of type I collagen in canine mammary carcinoma, finding longer and wider collagen fibers as well as an increase in stable collagen cross-links in neoplastic samples. Mass spectrometric analyses revealed over-hydroxylation of lysine residues in malignant mammary tumor samples, potentially promoting tumor cell metastasis. Furthermore, expression levels of genes encoding lysyl hydroxylase 2 (LH2) and its molecular chaperone FK506-binding protein 65 were significantly increased in neoplastic samples, suggesting a role in LH2-mediated stable collagen cross-links in promoting tumor cell metastasis.
SCIENTIFIC REPORTS
(2021)
Article
Chemistry, Medicinal
Md Sailful Islam, Cyrille C. Thinnes, James P. Holt-Martyn, Rasheduzzaman Chowdhury, Michael A. McDonough, Christopher J. Schofield
Summary: This study discusses the inhibition of human 2-oxoglutarate dependent oxygenase JMJD6, a cancer target, by 2-oxoglutarate mimics/competitors. NMR and mass spectrometry were used to monitor inhibitor binding and JMJD6-catalyzed lysine hydroxylation. Clinically applied prolyl hydroxylase inhibitors were found to also inhibit JMJD6, suggesting the potential for developing selective inhibitors for human oxygenases.
Article
Pharmacology & Pharmacy
Svetlana Galkina, Ekaterina A. Golenkina, Natalia Fedorova, Alexander L. Ksenofontov, Marina Serebryakova, Evgenii A. Arifulin, Vladimir Stadnichuk, Ludmila A. Baratova, Galina F. Sud'ina
Summary: Recent studies have shown that the development of depression involves inflammatory processes, while antidepressants have anti-inflammatory effects. Specifically, the antidepressant imipramine inhibits neutrophil adhesion and secretion, which could be a potential mechanism for its anti-inflammatory properties in depression.
FRONTIERS IN PHARMACOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Yoshihiro Ishikawa, Yuki Taga, Keith Zientek, Nobuyo Mizuno, Antti M. Salo, Olesya Semenova, Sara F. Tufa, Douglas R. Keene, Paul Holden, Kazunori Mizuno, Douglas B. Gould, Johanna Myllyharju, Hans Peter Bachinger
Summary: Collagen is the most abundant protein in humans, with a complex biosynthesis involving multiple enzymes and chaperones. LH1 and P3H3 play distinct but related roles in lysyl hydroxylation of collagen, with LH1 having a global enzymatic role and P3H3 being involved particularly at cross-link formation sites.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2021)
Article
Multidisciplinary Sciences
Wenhui Wu, Jeong Seon Kim, Aaron O. Bailey, William K. Russell, Stephen J. Richards, Tiantian Chen, Tingfei Chen, Zhenhang Chen, Bo Liang, Mitsuo Yamauchi, Houfu Guo
Summary: Humans and Acanthamoeba polyphaga mimivirus share numerous homologous genes, including collagens and collagen-modifying enzymes. Through genome-wide comparison, 52 new putative mimiviral proteins that are homologous with human proteins were identified. Collagens and collagen-modifying enzymes form the largest subnetwork in the functional network. Further analysis revealed a putative collagen glycosyltransferase R699, which showed high expression in Escherichia coli. The enzyme activity assay and mass spectrometric analyses suggested that R699 functions as a mimiviral collagen galactosylhydroxylysyl glucosyltransferase (GGT) using UDP-glucose as a sugar donor.
SCIENTIFIC REPORTS
(2022)
Article
Multidisciplinary Sciences
Rasheduzzaman Chowdhury, Martine Abboud, James Wiley, Anthony Tumber, Suzana Markolovic, Christopher J. Schofield
Summary: JMJD7, a JmjC oxygenase, functions as a lysyl hydroxylase and histone endopeptidase, and exhibits a conserved dimerization mode in fruit flies and humans. Studies on JMJD7 could facilitate the development of selective inhibitors for it and other JmjC oxygenases.
SCIENTIFIC REPORTS
(2022)
Article
Biochemistry & Molecular Biology
Mariya E. Semkova, J. Justin Hsuan
Summary: Excessive cross-linking of ECM by TGF beta has been identified as a major contributor to skin fibrosis in Systemic Sclerosis. The upregulation of lysyl-oxidase-like enzymes and transglutaminase in response to TGF beta treatment was confirmed. Additionally, alterations in the ECM cross-linking pattern induced by TGF beta, including the identification of new cross-linking sites between ECM proteins, were observed.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Multidisciplinary Sciences
Yuxin Tong, Yifei Qi, Gaofeng Xiong, Junyan Li, Timothy L. Scott, Jie Chen, Daheng He, Linzhang Li, Chi Wang, Andrew N. Lane, Ren Xu
Summary: Accumulation of succinate is associated with the progression of cancer. Succinate induces the mesenchymal phenotypes in mammary epithelial cells and enhances cancer cell stemness. Elevated succinate levels reduce the accumulation of 5-hydroxymethylcytosine and lead to the transcriptional repression of EMT-related genes.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2023)
Article
Medicine, Research & Experimental
Yuanli Ni, Jing Xu, Dali Tong
Summary: Prostate cancer is clinically heterogeneous and long-term treatment can lead to development of aggressive neuroendocrine phenotypes. The tumor immune microenvironment (TIME) is activated in the progression of prostate cancer. Our study suggests that JMJD6 may aid in alternative splicing of TGF beta mRNA, promoting TGF beta production and secretion and activating the TGF beta signaling pathway. Targeting JMJD6 at the transcription/mRNA splicing level could provide a novel therapeutic approach for blocking TGF beta production and improving immunotherapy efficacy.
MEDICAL HYPOTHESES
(2023)
Article
Biochemistry & Molecular Biology
Zihan Yang, Li Zhou, Tongxu Si, Siyuan Chen, Chengxi Liu, Kelvin Kaki Ng, Zesheng Wang, Zhiji Chen, Chan Qiu, Guopan Liu, Qingliang Wang, Xiaoyu Zhou, Liang Zhang, Zhongping Yao, Song He, Mengsu Yang, Zhihang Zhou
Summary: In this study, LH1 was found to promote the confined migration and metastasis of cancer cells by stabilizing SEPT2 and facilitating actin polymerization. These findings provide new insights into the migration and metastasis mechanisms of tumor cells.
Article
Cell Biology
Nicholas T. Crump, Andreas Hadjinicolaou, Meng Xia, John Walsby-Tickle, Uzi Gileadi, Ji-Li Chen, Mashiko Setshedi, Lars R. Olsen, I-Jun Lau, Laura Godfrey, Lynn Quek, Zhanru Yu, Erica Ballabio, Mike B. Barnkob, Giorgio Napolitani, Mariolina Salio, Hashem Koohy, Benedikt M. Kessler, Stephen Taylor, Paresh Vyas, James S. O. McCullagh, Thomas A. Milne, Vincenzo Cerundolo
Summary: Cancer cells evade immune recognition by synthesizing arginine while T cells fail to tolerate arginine depletion. T cell activation is compromised under arginine-depleted conditions due to incomplete chromatin remodeling and dysregulation of key genes. This highlights a T cell response to nutritional stress exploited by cancer cells for immune evasion.
Article
Biochemistry & Molecular Biology
Bernhard Luscher, Ivan Ahel, Matthias Altmeyer, Alan Ashworth, Peter Bai, Paul Chang, Michael Cohen, Daniela Corda, Francoise Dantzer, Matthew D. Daugherty, Ted M. Dawson, Valina L. Dawson, Sebastian Deindl, Anthony R. Fehr, Karla L. H. Feijs, Dmitri V. Filippov, Jean-Philippe Gagne, Giovanna Grimaldi, Sebastian Guettler, Nicolas C. Hoch, Michael O. Hottiger, Patricia Korn, W. Lee Kraus, Andreas Ladurner, Lari Lehtio, Anthony K. L. Leung, Christopher J. Lord, Aswin Mangerich, Ivan Matic, Jason Matthews, George-Lucian Moldovan, Joel Moss, Gioacchino Natoli, Michael L. Nielsen, Mario Niepel, Friedrich Nolte, John Pascal, Bryce M. Paschal, Krzysztof Pawlowski, Guy G. Poirier, Susan Smith, Gyula Timinszky, Zhao-Qi Wang, Jose Yelamos, Xiaochun Yu, Roko Zaja, Mathias Ziegler
Summary: ADP-ribosylation, a post-translational modification of proteins, nucleic acids, and metabolites, plays diverse roles in cellular processes such as stress responses, signaling, and transcriptional regulation. Recent advances in research have identified a wide range of cellular pathways regulated by ADP-ribosylation, highlighting the importance of understanding this mechanism in cell biology.
Article
Biochemistry & Molecular Biology
Lisa Schubert, Ivo A. Hendriks, Emil P. T. Hertz, Wei Wu, Selene Selles-Baiget, Saskia Hoffmann, Keerthana Stine Viswalingam, Irene Gallina, Satyakrishna Pentakota, Bente Benedict, Joachim Johansen, Katja Apelt, Martijn S. Luijsterburg, Simon Rasmussen, Michael Lisby, Ying Liu, Michael L. Nielsen, Niels Mailand, Julien P. Duxin
Summary: This study reveals an essential role of SCAI in ensuring error-free ICL repair upon activation of the FA pathway. SCAI forms a complex with Pol zeta and localizes to ICLs during DNA replication. In the absence of SCAI, HR-mediated ICL repair is defective, resulting in deletions and radial chromosomes.
Article
Biochemistry & Molecular Biology
Xu Zhao, Ivo A. Hendriks, Stephanie Le Gras, Tao Ye, Lucia Ramos-Alonso, Aurelie Nguea P, Guro Flor Lien, Fatemeh Ghasemi, Arne Klungland, Bernard Jost, Jorrit M. Enserink, Michael L. Nielsen, Pierre Chymkowitch
Summary: Sumoylation pathway plays a crucial role in adipocyte differentiation, supporting both the establishment of mature adipocyte transcriptional program and rewiring of transcriptional networks.
NUCLEIC ACIDS RESEARCH
(2022)
Article
Chemistry, Multidisciplinary
Mahmoud Moustafa, Mona G. Zaghloul, Mohamed A. Sabry, Walaa S. Aboelmaaty, Refaat B. Hamed, Sherif S. Ebada, Weaam Ebrahim
Summary: Four sesquiterpene lactones and beta-sitosterol were isolated from the methanol extract of Saussurea lappa roots. These compounds showed potential antiviral, antibacterial, and cytotoxic activities. Molecular docking studies suggested similar binding interactions as acyclovir for antiviral activity. The discovery of these compounds highlights their potential as therapeutic agents.
Article
Biochemistry & Molecular Biology
Simranjeet Kaur, Nok Yin Tam, Michael A. McDonough, Christopher J. Schofield, Wei Shen Aik
Summary: ALKBH5 is an enzyme responsible for demethylating RNA and has emerged as a potential target for cancer treatment. This study provides insight into the substrate recognition and demethylation mechanism of ALKBH5, and reveals its preference for specific sequences.
NUCLEIC ACIDS RESEARCH
(2022)
Review
Chemistry, Analytical
Judith B. Ngere, Kourosh H. Ebrahimi, Rachel Williams, Elisabete Pires, John Walsby-Tickle, James S. O. McCullagh
ANALYTICAL CHEMISTRY
(2023)
Article
Neurosciences
Azrul Abdul Kadir, Brianna J. Stubbs, Cher-Rin Chong, Henry Lee, Mark Cole, Carolyn Carr, David Hauton, James McCullagh, Rhys D. Evans, Kieran Clarke
Summary: Glucose and glycolysis play important roles in anaplerosis and beta HB oxidation in the heart. Glycogen, as a glucose store, can also contribute to anaplerosis. The study investigated the effects of glycogen content on beta HB oxidation and glycolytic rates in isolated rat hearts. Results showed that beta HB oxidation rates were lower in hearts with low glycogen content compared to high glycogen content, and beta HB oxidation inhibited glycolysis in all hearts. The findings suggest that glycogen facilitates cardiac beta HB oxidation and affects energetics.
JOURNAL OF PHYSIOLOGY-LONDON
(2023)
Article
Multidisciplinary Sciences
Pietro Fontana, Sara C. Buch-Larsen, Osamu Suyari, Rebecca Smith, Marcin J. Suskiewicz, Kira Schutzenhofer, Antonio Ariza, Johannes Gregor Matthias Rack, Michael L. Nielsen, Ivan Ahel
Summary: ADP-ribosylation signalling plays a crucial role in the DNA damage response of mammals, and its mechanism in fruit flies has been established using a multidisciplinary approach. Ser-ADPr is the major form of ADP-ribosylation in the DNA damage response of Drosophila melanogaster, and its formation depends on the dParp1:dHpf1 complex. The findings suggest that fruit flies are valuable model organisms to study the physiological role of Ser-ADPr signalling.
NATURE COMMUNICATIONS
(2023)
Article
Biochemistry & Molecular Biology
Emil P. T. Hertz, Ignacio Alonso-de Vega, Thomas Kruse, Yiqing Wang, Ivo A. Hendriks, Anna H. Bizard, Ania Eugui-Anta, Ronald T. Hay, Michael L. Nielsen, Jakob Nilsson, Ian D. Hickson, Niels Mailand
Summary: Hertz et al. use CRISPR screening to identify genetic vulnerabilities to inhibition of SUMOylation in human cells. They show that SUMO exerts its essential role in cell proliferation via NIP45- and BTRR-PICH-mediated DNA catenane resolution pathways. NIP45 mediates a TOP2-independent DNA catenane resolution process through its SUMO-like domains, promoting SUMOylation of specific factors including the SLX4 multi-nuclease complex, which contributes to catenane conversion into DSBs. Their findings establish the importance of SUMOylation in enabling resolution of toxic DNA catenanes via non-epistatic NIP45- and BTRR-PICH-dependent pathways to prevent mitotic failure.
NATURE STRUCTURAL & MOLECULAR BIOLOGY
(2023)
Review
Biology
A. S. Rebak, I. A. Hendriks, M. L. Nielsen
Summary: Citrullination is an important post-translational modification of arginine, with roles in autoimmune disorders, innate immunity response, and stem cell potency maintenance. However, our understanding of citrullination is not as comprehensive as other post-translational modifications. High-resolution mass spectrometry provides an unbiased approach to study citrullination and has already provided valuable insights. There is still untapped potential for proteome-wide investigations of citrullination using mass spectrometry approaches.
PHILOSOPHICAL TRANSACTIONS OF THE ROYAL SOCIETY B-BIOLOGICAL SCIENCES
(2023)
Article
Multidisciplinary Sciences
Meeli Mullari, Nicolas Fossat, Niels H. Skotte, Andrea Asenjo-Martinez, David T. Humphreys, Jens Bukh, Agnete Kirkeby, Troels K. H. Scheel, Michael L. Nielsen
Summary: The authors present the Brain-pCLAP methodology, identify the RBP atlas of the mouse brain, and demonstrate the differential binding of the splicing factor RBM5 to Huntington's disease relevant transcripts in R6/2 mice. Overall, they provide insights into the role of RBPs in RNA processing and their association with neurodegeneration. Rating: 8 points.
NATURE COMMUNICATIONS
(2023)
Article
Multidisciplinary Sciences
Frederick Richards, Marta J. Llorca-Cardenosa, Jamie Langton, Sara C. Buch-Larsen, Noor F. Shamkhi, Abhishek Bharadwaj Sharma, Michael L. Nielsen, Nicholas D. Lakin
Summary: The authors identify that PARP1 maintains genome integrity by regulating replication fork recovery through break-induced replication. Mechanistically, this is achieved through MRE11-dependent PARP1 activation and site-specific ADP-ribosylation of PolD3. PARP1 and PARP2 also have a novel role in regulating Rad52-dependent replication fork repair, suppressing replication-associated DNA damage, and maintaining genome stability.
NATURE COMMUNICATIONS
(2023)
Article
Chemistry, Multidisciplinary
Vicki L. Emms, Liam A. Lewis, Lilla Beja, Natasha F. A. Bulman, Elisabete Pires, Frederick W. Muskett, James S. O. Mccullagh, Lonnie. P. Swift, Peter J. Mchugh, Richard J. Hopkinson
Summary: Research on formaldehyde is hindered by its reactivity and volatility. A new set of compounds have been developed as formaldehyde delivery agents, which have shown potential for cancer therapeutics.
Review
Cell Biology
Ingvild Comfort Hvinden, Tom Cadoux-Hudson, Christopher J. Schofield, James S. O. McCullagh
Summary: Mutations in metabolic genes IDH1 and IDH2 are commonly found in human cancers, affecting cellular processes and potentially influencing tumorigenesis and treatment outcomes.
CELL REPORTS MEDICINE
(2021)