Article
Cell Biology
Wenxiang Hu, Chunjie Jiang, Mindy Kim, Yang Xiao, Hannah J. Richter, Dongyin Guan, Kun Zhu, Brianna M. Krusen, Arielle N. Roberts, Jessica Miller, David J. Steger, Mitchell A. Lazar
Summary: This study provides insights into the specific metabolic functions of PPAR gamma isoforms, suggesting that they can be targeted for improving therapy for insulin resistance and diabetes.
GENES & DEVELOPMENT
(2022)
Article
Biochemistry & Molecular Biology
Andrew J. Modzelewski, Wanqing Shao, Jingqi Chen, Angus Lee, Xin Qi, Mackenzie Noon, Kristy Tjokro, Gabriele Sales, Anne Biton, Aparna Anand, Terence P. Speed, Zhenyu Xuan, Ting Wang, Davide Risso, Lin He
Summary: Retrotransposons play a crucial role in gene regulation during mammalian preimplantation development, with species-specific transposon promoters generating alternative protein isoforms that impact cell proliferation. The unique expression of Cdk2ap1(Delta N) in preimplantation embryos of each mammalian species correlates with the duration of preimplantation development.
Article
Biochemistry & Molecular Biology
Sara B. Linker, Inigo Narvaiza, Jonathan Y. Hsu, Meiyan Wang, Fan Qiu, Ana P. D. Mendes, Ruth Oefner, Kalyani Kottilil, Amandeep Sharma, Lynne Randolph-Moore, Eunice Mejia, Renata Santos, Maria C. Marchetto, Fred H. Gage
Summary: Human neurodevelopment is slower than that in other nonhuman primates, a phenomenon referred to as neoteny. The transcription factor GATA3 plays a unique role in human neuronal maturation, and downregulation of GATA3 accelerates the speed of developing action potentials, modulating the human neotenic phenotype.
Article
Reproductive Biology
Yanqiu Dong, Lanjie Jin, Xiaoqian Liu, Dongjie Li, Weina Chen, Haonan Huo, Cui Zhang, Shijie Li
Summary: The study assessed the allelic expression of bovine IMPACT, OSBPL1A, and HRH4 genes and examined the differentially methylated regions (DMRs) associated with these genes. The results revealed isoform-specific monoallelic expression of IMPACT and OSBPL1A genes in bovine adult tissues, while HRH4 gene showed biallelic expression. Additionally, DMRs were identified in the promoter region of OSBPL1A gene and DNA methylation seemed to be correlated with the expression of HRH4 gene in tissues.
Article
Psychiatry
Asbjorn Holmgren, Lars Hansson, Kristine Bjerkaas-Kjeldal, Agata Antonia Rita Impellizzeri, Gregor D. Gilfillan, Srdjan Djurovic, Timothy Hughes
Summary: The study identified a splice form associated with BD, which showed significant expression differences in different brain regions. This suggests a potential role of this splice form in myelin maturation in the human brain.
TRANSLATIONAL PSYCHIATRY
(2022)
Article
Cell Biology
Partho Sen, Syed Bilal Ahmad Andrabi, Tanja Buchacher, Mohd Moin Khan, Ubaid Ullah Kalim, Tuomas Mikael Lindeman, Marina Amaral Alves, Victoria Hinkkanen, Esko Kemppainen, Alex M. Dickens, Omid Rasool, Tuulia Hyotylainen, Riitta Lahesmaa, Matej Oresic
Summary: The study demonstrates specific metabolic changes in human CD4(+) T cells during activation and functional differentiation, highlighting the importance of the de novo sphingolipid pathway in Th17 cell differentiation and effector functions, with serine palmitoyltransferase playing a significant role in the expression of proinflammatory cytokines IL-17A and IL17F by Th17 cells. These findings offer a comprehensive resource for selectively manipulating CD4(+) T cells in conditions characterized by an imbalance of Th17/natural Treg (nTreg) cells.
Article
Cell Biology
Dong-Jiunn Jeffery Truong, Teeradon Phlairaharn, Bianca Esswein, Christoph Gruber, Deniz Tuemen, Eniko Baligacs, Niklas Armbrust, Francesco Leandro Vaccaro, Eva-Maria Lederer, Eva Magdalena Beck, Julian Geilenkeuser, Simone Goeppert, Luisa Krumwiede, Christian Graetz, Gerald Raffl, Dominic Schwarz, Martin Zirngibl, Milica Zivanic, Maren Beyer, Johann Dietmar Koerner, Tobias Santl, Valentin Evsyukov, Tabea Strauss, Sigrid C. Schwarz, Guenter U. Hoeglinger, Peter Heutink, Sebastian Doll, Marcus Conrad, Florian Giesert, Wolfgang Wurst, Gil Gregor Westmeyer
Summary: A cell-based reporter system named EXSISERS was developed by Truong et al., allowing non-invasive quantification of protein expression levels of exon-specific isoforms via intein-mediated protein splicing. This system enables non-disruptive and multimodal monitoring of exon-specific isoform expression with high sensitivity and cellular resolution, as well as high-throughput screening of exon-specific therapeutic interventions.
NATURE CELL BIOLOGY
(2021)
Article
Biology
Marc Catalan-Garcia, Francois Chauvigne, Jon Anders Stavang, Frank Nilsen, Joan Cerda, Roderick Nigel Finn
Summary: The study examines the evolutionary divergence of aquaglyceroporins (GLPs) in copepods, revealing high rates of gene duplication across species. They also observe tissue- and sex-specific expression of GLP splice variants in the parasitic copepod, L. salmonis, with subsequent PKA- or PKC-dependent changes in membrane trafficking. These findings suggest that mutations in GLP genes regulating intracellular trafficking may play a role in neofunctionalization in copepods.
COMMUNICATIONS BIOLOGY
(2021)
Article
Virology
Wing-Hang Ip, Britta Wilkens, Anastasia Solomatina, Judith Martin, Michael Melling, Paloma Hidalgo, Luca D. Bertzbach, Thomas Speiseder, Thomas Dobner
Summary: The E1 transcription unit of adenovirus type 5 encodes regulatory proteins essential for viral replication and transformation. Cellular factor FAM111B is found to be highly regulated in an E1A-dependent manner during HAdV-C5 infections, and its knockdown increases viral replication, indicating its role as an anti-adenoviral host factor. These findings suggest that FAM111B may play a crucial role in the host antiviral immune response against HAdV-C5.
Article
Multidisciplinary Sciences
Eric M. Lynch, Michael A. DiMattia, Steven Albanese, Gydo C. P. van Zundert, Jesse M. Hansen, Joel D. Quispe, Madison A. Kennedy, Andreas Verras, Kenneth Borrelli, Angela Toms, Neelu Kaila, Kevin D. Kreutter, Joshua J. McElwee, Justin M. Kollman
Summary: CTPS1 is essential for an effective immune response, with deficiency leading to severe immunodeficiency. CTPS1 expression is up-regulated in activated lymphocytes to meet the increased demand for nucleic acid and lipid synthesis. Selective inhibition of CTPS1 could be beneficial for treating immune disorders and lymphocyte cancers, with recent small-molecule inhibitors showing promise in inhibiting proliferation of human T cells.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Article
Medicine, Research & Experimental
Costanza Lo Cascio, James B. McNamara, Ernesto L. Melendez, Erika M. Lewis, Matthew E. Dufault, Nader Sanai, Christopher L. Plaisier, Shwetal Mehta
Summary: This study highlights the important role of HDAC1 in glioblastoma and the necessity to develop isoform-specific drugs targeting glioma stem cells.
Article
Multidisciplinary Sciences
Mikihito Shibata, Kartik Pattabiraman, Sydney K. Muchnik, Navjot Kaur, Yury M. Morozov, Xiaoyang Cheng, Stephen G. Waxman, Nenad Sestan
Summary: Comparative analysis of human and macaque transcriptomic data identified transient upregulation of CBLN2 gene expression in the prefrontal cortex during midfetal development, coinciding with synaptogenesis initiation. Species differences in CBLN2 expression and laminar distribution may be partly due to Hominini-specific deletions containing SOX5-binding sites within a retinoic acid-responsive CBLN2 enhancer. Humanization of the mouse Cbln2 enhancer promotes increased and ectopic Cbln2 expression, suggesting a genetic and molecular basis for the disproportionate increase in dendritic spines in the Hominini prefrontal cortex and its potential linkage to neuropsychiatric disorder pathogenesis.
Article
Multidisciplinary Sciences
Margarete Diaz-Cuadros, Teemu P. Miettinen, Owen S. Skinner, Dylan Sheedy, Carlos Manlio Diaz-Garcia, Svetlana Gapon, Alexis Hubaud, Gary Yellen, Scott R. Manalis, William M. Oldham, Olivier Pourquie
Summary: Animals display inter-species variation in embryonic development rates, with differences in biochemical reaction rates being thought responsible for species-specific rates. This study establishes an in vitro system using pluripotent stem cells to simulate the twofold difference in developmental rates between mouse and human embryos. The mass-specific metabolic rates were found to scale with developmental rate, higher in mouse cells than in human cells. Manipulating metabolic rates could control developmental rate and have translational applications.
Article
Multidisciplinary Sciences
Shreyas Jadhav, Sudipta Tripathi, Anil Chandrekar, Sushrut S. Waikar, Li-Li Hsiao
Summary: The study identified two circulating isoforms of alpha Klotho and developed an antibody using a unique 15aa peptide sequence to specifically detect the secreted isoform in human plasma. This finding will enhance the potential of alpha Klotho isoforms as biomarkers for CKD and other conditions by facilitating the distinguishing of their levels in circulation.
Review
Biochemistry & Molecular Biology
Saurabh Tiwari, Gayathri Rajamanickam, Veena Unnikrishnan, Mina Ojaghi, John P. Kastelic, Jacob C. Thundathil
Summary: An advanced understanding of sperm function is important for male fertility prediction and addressing male infertility. Current methods for evaluating fertility overlook subtle differences in sperm, and research is now focused on developing in vitro sperm function tests and identifying biomarkers. This review discusses the role of the ATP1A4 protein in capacitation and fertilization events, and its potential use in improving male fertility prediction.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Biochemistry & Molecular Biology
Wing Hang Ip, Thomas Dobner
Article
Chemistry, Multidisciplinary
Samuel Hofmann, Julia Mai, Sawinee Masser, Peter Groitl, Alexander Herrmann, Thomas Sternsdorf, Ruth Brack-Werner, Sabrina Schreiner
Editorial Material
Biochemistry & Molecular Biology
Ronald T. Hay
Summary: The global pandemic has greatly affected public health and economies, highlighting the need for effective antiviral drugs. Research has identified potential antiviral candidate drugs through the development of biochemical assays and screening of drug libraries.
BIOCHEMICAL JOURNAL
(2021)
Article
Virology
Wing-Hang Ip, Britta Wilkens, Anastasia Solomatina, Judith Martin, Michael Melling, Paloma Hidalgo, Luca D. Bertzbach, Thomas Speiseder, Thomas Dobner
Summary: The E1 transcription unit of adenovirus type 5 encodes regulatory proteins essential for viral replication and transformation. Cellular factor FAM111B is found to be highly regulated in an E1A-dependent manner during HAdV-C5 infections, and its knockdown increases viral replication, indicating its role as an anti-adenoviral host factor. These findings suggest that FAM111B may play a crucial role in the host antiviral immune response against HAdV-C5.
Article
Biology
Luca D. Bertzbach, Wing-Hang Ip, Thomas Dobner
Summary: Animal models play an important role in human adenovirus research, with various species tested for susceptibility to human adenovirus infection and some rodents shown to develop tumors post-infection. Current animal models for studying HAdV pathogenesis, persistence, and tumorigenesis include Syrian hamsters, mice, and cotton rats.
Article
Virology
Marie Fiedler, Wing-Hang Ip, Helga Hofmann-Sieber, Britta Wilkens, Francis K. Nkrumah, Wenli Zhang, Anja Ehrhardt, Luca D. Bertzbach, Thomas Dobner
Summary: The human adenovirus type C5 (HAdV-C5) E1B-55K protein is a multifunctional regulator of HAdV-C5 replication, with phosphorylation and SUMO conjugation playing important roles in its functions. The interaction between E1B-55K and E4orf6 inhibits SUMOylation of E1B-55K, which may promote viral replication.
Article
Microbiology
Jana Boddin, Wing-Hang Ip, Britta Wilkens, Konstantin von Stromberg, Wilhelm Ching, Emre Koyuncu, Luca D. Bertzbach, Thomas Dobner
Summary: This study reveals the significant impact of single amino acid exchange mutations in the DNA binding protein of human adenovirus on viral replication. The interactions with the cellular ubiquitination machinery and the formation of viral replication centers are crucial steps that are affected by these mutations. This research has implications for the optimization of adenoviral vectors and the development of anti-adenoviral compounds.
Article
Virology
Margarita Valdes Aleman, Luca D. Bertzbach, Thomas Speiseder, Wing Hang Ip, Ramon A. Gonzalez, Thomas Dobner
Summary: During human adenovirus infection, the late phase of viral replication results in a significant increase in viral late mRNA abundance, which outcompetes cellular mRNA biogenesis rather than selectively exporting viral mRNA.
Article
Cell Biology
Ellis G. Jaffray, Michael H. Tatham, Barbara Mojsa, Magda Liczmanska, Alejandro Rojas-Fernandez, Yili Yin, Graeme Ball, Ronald T. Hay
Summary: Jaffray et al. demonstrated that the degradation of PML and PML-RARA induced by arsenic relies on the VCP/p97 segregase protein. Arsenic trioxide treatment leads to degradation of PML-RARA and PML, curing the disease. The UFD1-NPLOC4-p97 segregase complex is essential for extracting poly-ubiquitinated, poly-SUMOylated PML from PML bodies prior to proteasomal degradation.
JOURNAL OF CELL BIOLOGY
(2023)
Article
Microbiology
Lilian Goettig, Christina Weiss, Miona Stubbe, Lisa Hanrieder, Samuel Hofmann, Alessandro Grodziecki, Daniela Stadler, Arnaud Carpentier, Ulrike Protzer, Sabrina Schreiner
Summary: Apobec3A is upregulated during HAdV infection and its stabilization is mediated by viral proteins E1B-55K and E4orf6, leading to limited HAdV replication through a deaminase-dependent mechanism. Silencing Apobec3A enhances adenoviral replication. HAdV triggers Apobec3A dimerization and increases its activity to repress the virus by disrupting viral replication centers.
Article
Virology
Wing-Hang Ip, Michael H. Tatham, Steewen Krohne, Julia Gruhne, Michael Melling, Tina Meyer, Britta Gornott, Luca D. Bertzbach, Ronald T. Hay, Estefania Rodriguez, Thomas Dobner
Summary: This study used quantitative SUMO proteomics to analyze the cellular consequences of E1B-55K-mediated host cell modulation and adenovirus infection. The results showed that changes in the SUMOylated proteome could regulate DNA damage response, cell cycle control, chromatin assembly, and gene transcription. Additionally, a SUMO-dependent, ubiquitin-mediated degradation mechanism for some SUMO substrates was identified, suggesting that E1B-55K might use multiple mechanisms to alter restrictive cellular pathways.
JOURNAL OF VIROLOGY
(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)
Article
Cell Biology
Magda Liczmanska, Michael H. Tatham, Barbara Mojsa, Ania Eugui-Anta, Alejandro Rojas-Fernandez, Adel F. M. Ibrahim, Ronald T. Hay
Summary: The small ubiquitin-like modifier (SUMO) protease SENP6 disassembles SUMO chains from cellular substrate proteins. Proteins of the lamin family show increased SUMO modification after SENP6 depletion, accompanied by nuclear structural changes similar to laminopathies. Proximity-induced SUMO modification (PISM) directly targets lamin A/C for SUMO conjugation, recapitulating altered nuclear structure after SENP6 depletion. SENP6 activity protects the nucleus against hyperSUMOylation-induced laminopathy-like alterations.
Article
Virology
Viktoria Kolbe, Wing H. Ip, Lisa Kieweg-Thompson, Judith Lang, Julia Gruhne, Tina Meyer, Britta Wilkens, Marcel Schie, Roland Thunauer, Sabrina Schreiner, Luca D. Bertzbach, Estefania Rodriguez, Thomas Dobner
Summary: This research identified potential SUMO-conjugation motifs in E1B-55K proteins from HAdV species A to F and demonstrated that these proteins are SUMOylated at a highly conserved lysine residue. The study also revealed that E1B-55K SUMOylation regulates intracellular localization and p53-mediated transcription in most HAdV species.
JOURNAL OF VIROLOGY
(2022)