Article
Cell Biology
Sugako Ogushi, Ahmed Rattani, Jonathan Godwin, Jean Metson, Lothar Schermelleh, Kim Nasmyth
Summary: Protection of near-centromeric REC8 cohesin and sister kinetochore co-orientation depend on spindle-chromosome complexes (SCCs) in meiosis I, while being lost in meiosis II, resulting in sister chromatid disjunction and production of haploid gametes. The catalytic activity of Separase is crucial for converting kinetochores to a bi-oriented state and deprotecting cohesin in meiosis I.Selective cleavage of REC8 near kinetochores is sufficient to disrupt co-orientation in univalent chromosomes, but may require resolution of chiasmata in bivalents.
DEVELOPMENTAL CELL
(2021)
Article
Biochemistry & Molecular Biology
Jothi Anantharajan, Nithya Baburajendran, Grace Lin, Yong Yao Loh, Weijun Xu, Nur Huda Binte Ahmad, Shuang Liu, Anna E. Jasson, John Wee Liang Kuan, Elizabeth Yihui Ng, Yee Khoon Yeo, Alvin W. Hung, Joma Joy, Jeffrey Hill, Heide L. Ford, Rui Zhao, Thomas H. Keller, CongBao Kang
Summary: This study demonstrated that the inhibitor-bound form of EYA2 does not favor binding to Mg2+, essential for its Tyr phosphatase activity, and described the optimization and characterization of allosteric inhibitors. Through synthesis of analogues, potency of inhibitors was improved and structure-activity relationships were elucidated. Co-crystal structures confirmed binding modes of inhibitors, providing insight into molecular interactions and potential for structure-based drug discovery.
Article
Biochemistry & Molecular Biology
Jianong Zhang, Liang Zhang, Ji Nie, Yan Lin, Yao Li, Wei Xu, Jian-Yuan Zhao, Shi-Min Zhao, Chenji Wang
Summary: Calcineurin interacts with the mitochondrial gatekeeper enzyme PDC to enhance cellular metabolism and suppress cancer cell proliferation. Inhibition of the calcineurin-PDC pathway by CNIs may promote tumorigenesis, suggesting a potential mechanism for the increased cancer incidence in transplant recipients.
Article
Cell Biology
Sabrina Klemz, Thomas Wallach, Sandra Korge, Mechthild Rosing, Roman Klemz, Bert Maier, Nicholas C. Fiorenza, Irem Kaymak, Anna K. Fritzsche, Erik D. Herzog, Ralf Stanewsky, Achim Kramer
Summary: In organisms with circadian clocks, the post-translational modifications of clock proteins, particularly phosphorylation, play a crucial role in controlling circadian rhythms. Protein phosphatase 4 (PPP4) and its regulatory subunit PPP4R2 have been identified as critical components in mammals and Drosophila, affecting the circadian system by regulating phosphorylation and transactivation activity of CLOCK/BMAL1.
GENES & DEVELOPMENT
(2021)
Article
Biochemistry & Molecular Biology
Alberto Garcia-Nieto, Amrita Patel, Yan Li, Roel Oldenkamp, Leonardo Feletto, Joshua J. Graham, Laureen Willems, Kyle W. Muir, Daniel Panne, Benjamin D. Rowland
Summary: In the early stages of mitosis, SGO1 protects centromeric cohesin to maintain sister chromatid cohesion until all chromosomes are properly attached to the mitotic spindle. The crystal structure of human SGO1 bound to cohesin reveals a binding interface shared with CTCF, suggesting a universal mechanism of cohesin control. This SGO1-cohesin interaction is essential for centromere localization and protection against WAPL-mediated cohesin release, ensuring faithful chromosome segregation and a stable karyotype.
NATURE STRUCTURAL & MOLECULAR BIOLOGY
(2023)
Review
Food Science & Technology
Carina Proenca, Daniela Ribeiro, Marisa Freitas, Felix Carvalho, Eduarda Fernandes
Summary: Type 2 diabetes is a growing global health problem caused by insulin secretion defects and/or insulin resistance. The role of protein tyrosine phosphatase 1B and dipeptidyl peptidase-4 in T2D has attracted scientific attention, with a focus on the potential of flavonoids as therapeutic agents. Studies have explored the inhibitory effects of flavonoids on PTP1B and DPP-4 activities, aiming to discover compounds with improved potential for treating T2D.
CRITICAL REVIEWS IN FOOD SCIENCE AND NUTRITION
(2022)
Article
Biochemistry & Molecular Biology
Owen K. Smith, Charles Limouse, Kelsey A. Fryer, Nicole A. Teran, Kousik Sundararajan, Rebecca Heald, Aaron F. Straight
Summary: The study successfully identified the repetitive sequences of Xenopus laevis centromeres using a combination of Cenpa ChIP-seq and k-mer analysis, and mapped the centromere positions on each chromosome through in situ hybridization and analysis of centromere-enriched k-mers distribution. This approach enables previously unapproachable centromere genomic studies and could be broadly applicable for analyzing repetitive sequences in any organism.
Article
Biochemistry & Molecular Biology
Shuhei Ishikura, Kazumasa Yoshida, Sayuri Hashimoto, Kazuhiko Nakabayashi, Toshiyuki Tsunoda, Senji Shirasawa
Summary: This study demonstrates the essential role of the centromeric protein CENP-B in the localization of ZFAT to the centromere for regulating ncRNA transcription. Depletion of CENP-B leads to reduced levels of ZFAT protein at the centromere and decreased expression of ncRNA, highlighting the involvement of CENP-B in ZFAT-mediated centromeric functions.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2021)
Article
Medicine, Research & Experimental
Martina Cusan, Haifeng Shen, Bo Zhang, Aijun Liao, Lu Yang, Meiling Jin, Mike Fernandez, Prajish Iyer, Yiming Wu, Kevyn Hart, Catherine Gutierrez, Sara Nik, Shondra M. Pruett-Miller, Jeremy Stark, Esther A. Obeng, Teresa Bowman, Catherine J. Wu, Ren-Jang Lin, Lili Wang
Summary: This research discovers that the mutation of RNA splicing factor SF3B1 results in the accumulation of centromeric R-loops, leading to increased chromosomal oscillation, impaired chromosome segregation, altered spindle architecture, and aneuploidy. The study reveals the relationship between dysregulated RNA splicing and chromosomal instability and highlights the role of centromeric R-loop augmentation in leukemogenesis.
JOURNAL OF CLINICAL INVESTIGATION
(2023)
Article
Cell Biology
Patrick Ehm, Nina Nelson, Susanne Giehler, Matthias Schaks, Bettina Bettin, Johannes Kirchmair, Manfred Juecker
Summary: This study investigated patient-derived mutations in the phosphatase domain of SHIP1 and found that two mutations had reduced protein expression and enzymatic activity, while two other mutations had reduced activity but comparable expression levels. Overall, the mutations significantly affected the PI3K/AKT/mTOR pathway, either by decreasing SHIP1 activity or expression.
CELLULAR SIGNALLING
(2023)
Article
Chemistry, Medicinal
Ying Yang, Lei Zhang, Jinying Tian, Fei Ye, Zhiyan Xiao
Summary: A hierarchical virtual screening identified four potential PTP1B inhibitors with distinct structures, among which H3 and H9 showed selectivity to PTP1B. Key residues responsible for potent allosteric inhibition and excellent PTP selectivity were identified through molecular dynamics simulations and MM-GBSA calculations, aiding future molecular design of PTP1B allosteric inhibitors.
JOURNAL OF CHEMICAL INFORMATION AND MODELING
(2021)
Article
Immunology
Xiaowen Bi, Baolin Jiang, Jinyi Zhou, Xirui Fan, Xintong Yan, Juanjuan Liang, Lan Luo, Zhimin Yin
Summary: Inhibition of CBP bromodomain effectively blocks HMGB1-mediated inflammatory responses and reduces its pro-inflammatory activity. SGC-CBP30 down-regulates the activation of relevant signaling pathways to decrease the inflammatory effects of HMGB1.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Kentaro Ohkuni, Loran Gliford, Wei-Chun Au, Evelyn Suva, Peter Kaiser, Munira A. Basrai
Summary: This study demonstrates that Cdc48 and its cofactors Ufd1 and Npl4 facilitate the removal of mislocalized Cse4 from non-centromeric chromatin. Defects in this mechanism may contribute to CIN in human cancers.
NUCLEIC ACIDS RESEARCH
(2022)
Article
Biology
Alexandra Papaioannou, Federica Centonze, Alice Metais, Marion Maurel, Luc Negroni, Matias Gonzalez-Quiroz, Sayyed Jalil Mahdizadeh, Gabriella Svensson, Ensieh Zare, Alice Blondel, Albert C. Koong, Claudio Hetz, Remy Pedeux, Michel L. Tremblay, Leif A. Eriksson, Eric Chevet
Summary: The IRE1 alpha RNase regulatory network is dynamically regulated by tyrosine kinases and phosphatases. The extent of RtcB tyrosine phosphorylation determines cell adaptive or death outputs.
LIFE SCIENCE ALLIANCE
(2022)
Review
Biochemistry & Molecular Biology
Ana E. F. Ferreira, Joana Santiago, Joana V. V. Silva, Pedro E. F. Oliveira, Margarida Fardilha
Summary: This review provides an overview of the protein phosphorylation-dependent biochemical pathways underlying sperm motility acquisition and hyperactivation, as well as the research advances in PP inhibitors. Further research in this area, particularly using other PP inhibitors, is necessary due to the increasing cases of male infertility.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Biochemistry & Molecular Biology
Csaba Bajusz, Ildiko Kristo, Csilla Abonyi, Tomas Venit, Viktor Vedelek, Tamas Lukacsovich, Attila Farkas, Peter Borkuti, Zoltan Kovacs, Izabella Bajusz, Annamaria Marton, Csaba Vizler, Zoltan Lipinszki, Rita Sinka, Piergiorgio Percipalle, Peter Vilmos
Summary: By reducing the amount of Moesin in the nuclei of Drosophila, the study demonstrated the importance of ERM proteins in the nucleus, resulting in developmental defects and revealing their regulatory role in gene expression.
Article
Multidisciplinary Sciences
Zuzana Hodakova, Andrea Nans, Simone Kunzelmann, Shahid Mehmood, Ian Taylor, Frank Uhlmann, Peter Cherepanov, Martin R. Singleton
Summary: Chl1 is a member of the XPD family of 5'-3' DNA helicases, with unique structural features that play a crucial role in chromosome segregation in yeast. The insert domain in Chl1 regulates its DNA binding.
Article
Multidisciplinary Sciences
Ruifang Guan, Tengfei Lian, Bing-Rui Zhou, Emily He, Carl Wu, Martin Singleton, Yawen Bai
Summary: The study reveals the structures of the budding yeast centromeric nucleosome and the CBF3 core, providing insights into how the CBF3 complex guides the formation of the centromeric nucleosome.
NATURE COMMUNICATIONS
(2021)
Article
Cell Biology
Margaux R. Audett, Erin L. Johnson, Jessica M. McGory, Dylan M. Barcelos, Evelin Oroszne Szalai, Marcin R. Przewloka, Thomas J. Maresca
Summary: The N-terminal region (NTR) of KNL1 binds microtubules (MTs) and recruits PP1-87B, while the central disordered region binds SAC proteins through Aurora B kinase phosphorylation, providing a regulatory mechanism for SAC signaling during cell division in Drosophila melanogaster.
MOLECULAR BIOLOGY OF THE CELL
(2022)
Article
Biochemistry & Molecular Biology
Balint Csoboz, Imre Gombos, Zoltan Kota, Barbara Dukic, Eva Klement, Vanda Varga-Zsiros, Zoltan Lipinszki, Tibor Pali, Laszlo Vigh, Zsolt Torok
Summary: In this study, the interaction between HSPB1 and phospholipids was characterized, revealing that HSPB1 associates with membrane-forming lipids and has a strong affinity towards highly fluid membranes. HSPB1 modulates the physical properties of interacting membranes by altering lipid mobility and greatly affects the phase behavior of the plasma membrane under membrane fluidizing stress conditions. These findings suggest a new function for HSPB1 as a membrane chaperone.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Virology
Tunde Kartali, Nora Zsindely, Ildiko Nyilasi, Orsolya Nemeth, Sandor Kocsube, Zoltan Lipinszki, Roland Patai, Krisztina Spisak, Gabor Nagy, Laszlo Bodai, Csaba Vagvolgyi, Tamas Papp
Summary: The presence of viruses in Mucoromycota, a fungal group, has been less studied compared to other fungal groups. In this study, we identified 11 novel dsRNA viruses in different Umbelopsis strains and characterized their genomes. These viruses belong to the genus Totivirus or are related to Totiviridae. The presence of virus particles in the examined fungal strains was confirmed by transmission electron microscopy.
Article
Biochemistry & Molecular Biology
Zsuzsanna Rethi-Nagy, Edit Abraham, Zoltan Lipinszki
Summary: This method involves immobilizing the protein/domain of interest to a carrier, incubating it with a labelled putative binding partner, and visualizing the interacting proteins through SDS/PAGE autoradiography, offering a simple, cheap, and easily performed in vitro analysis suitable for wet labs.
Article
Biochemistry & Molecular Biology
Peter Borkuti, Ildiko Kristo, Aniko Szabo, Csaba Bajusz, Zoltan Kovacs, Zsuzsanna Rethi-Nagy, Zoltan Lipinszki, Tamas Lukacsovich, Sven Bogdan, Peter Vilmos
Summary: Actin, a fundamental protein, plays various roles in the nucleus and cytoplasm of eukaryotic cells. Our study in Drosophila revealed the essentiality of nuclear actin and the robustness of its nuclear localization, supported by a strong system. We also identified novel nuclear import factors specific to actin, shedding light on the mechanism behind its nuclear functions.
FRONTIERS IN MOLECULAR BIOSCIENCES
(2022)
Article
Biochemistry & Molecular Biology
Edit Abraham, Zsuzsanna Rethi-Nagy, Peter Vilmos, Rita Sinka, Zoltan Lipinszki
Summary: Protein phosphatase 5 (PP5) is a conserved enzyme involved in regulating important cellular processes in eukaryotes. It interacts with and dephosphorylates the Polo-like kinase 4 (Plk4), a key regulator of centriole duplication in animal cells. PP5 and Plk4 co-localize at the centrosomes and PP5 loss reduces fertility in animals.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Biochemistry & Molecular Biology
Gianluca Amadei, David M. M. Glover
Summary: Studies have found that stem cells can self-assemble in the culture dish to mimic early embryonic development. These stem cell-derived models can imitate cell movements and gene expression patterns of gastrulation, and even develop into different organs and tissues. This article explores the journey of discovering and understanding these stem cell capabilities.
Article
Biology
Levente Kovacs, Agnieszka Fatalska, David M. Glover
Summary: In this study, a 24-amino-acid sequence from the tail anchor domain of the Drosophila proapoptotic protein Hid was used to target exogenous proteins to the mitochondria in Drosophila cells. It was found that Drosophila Sas6 can bind both Drosophila Gorab and its human GORAB ortholog, whereas human SAS6 is unable to bind either GORAB or Gorab. These findings are discussed in relation to the evolutionary conservation of Gorab and the divergence of Sas6.
Article
Multidisciplinary Sciences
Kirsten I. Verster, Gyoengyi Cinege, Zoltan Lipinszki, Lilla B. Magyar, Eva Kurucz, Rebecca L. Tarnopol, Edit Abraham, Zsuzsanna Darula, Marianthi Karageorgi, Josephine A. Tamsil, Saron M. Akalu, Istvan Ando, Noah K. Whiteman
Summary: Toxin cargo genes can be transferred horizontally between bacterial species through phages and play a crucial role in bacterial pathogenesis evolution. This study found that these genes have also been transferred from phage or bacteria to animals, resulting in novel adaptations. Through horizontal gene transfer, bacterial genes encoding toxins of animal cells have been captured by insect genomes. These genes and their encoded proteins were found to be expressed by immune cells in insects and played a role in resistance against parasitoid wasps. The findings suggest that phage or bacterially derived eukaryotic toxin genes can drive the rapid evolution of novelty in animals.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2023)
Review
Biology
A. L. Sperling, D. M. Glover
Summary: Parthenogenesis is widely observed in animals, but remains understudied. In dipterans, it is of particular importance due to the presence of parthenogenetic species that are disease vectors and agricultural pests. This study presents a catalog of parthenogenetic dipterans, explores the genetic basis of parthenogenesis, and discusses the evolutionary significance of parthenogenesis in this order.
PROCEEDINGS OF THE ROYAL SOCIETY B-BIOLOGICAL SCIENCES
(2023)
Article
Cell Biology
Zsuzsanna Rethi-Nagy, Edit Abraham, Rita Sinka, Szilvia Juhasz, Zoltan Lipinszki
Summary: This study investigated the interaction between PP4 and CNTRB in HR-mediated DNA repair in human cells, revealing the importance of specific motifs in CNTRB for the repair process.
Article
Biochemistry & Molecular Biology
Zsuzsanna Rethi-Nagy, Edit Abraham, Katalin Udvardy, Eva Klement, Zsuzsanna Darula, Margit Pal, Robert L. Katona, Vilmos Tubak, Tibor Pali, Zoltan Kota, Rita Sinka, Andor Udvardy, Zoltan Lipinszki
Summary: In this study, we identified and characterized a 13-mer protein segment derived from the p54/Rpn10 ubiquitin receptor subunit of the Drosophila 26S proteasome, named STABILON. Attachment of STABILON to unstable proteins significantly increased their concentration, and STABILON also acted as a dual function motif by increasing the concentration of corresponding mRNAs and preventing degradation of short-lived fusion proteins.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)