Article
Agriculture, Multidisciplinary
Biying Wang, Xiaoya Zhao, Tong Fu, Xiaoyi Chen, Xiaoyu Guo, Xianzhen Li, Fan Yang
Summary: A positively evolved Suc2 promoter (SUC 2p) with stronger promoter activity than the wild-type Suc2 promoter (SUC 2wtp) was obtained in this study. The strength of SUC 2p was modulated by different glucose concentrations, with significantly enhanced promoter activity at low glucose concentrations.
JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
(2023)
Article
Microbiology
Tianyu Zhao, Asaka Chida, Yuichi Shichino, Dongwoo Choi, Masaki Mizunuma, Shintaro Iwasaki, Yoshikazu Ohya
Summary: This study reveals the global translational regulation during replicative aging in yeast using ribosome profiling technique. The research found that the translational efficiency of genes involved in DNA repair and chromosome organization increased, while the translational efficiency of genes encoding ribosome components, transposons and cell wall assembly decreased during replicative aging.
Article
Multidisciplinary Sciences
Weijing Yao, Yixing Li, Yingcong Chen, Yuting Chen, Pengwei Zhao, Yi Zhang, Qiang Jiang, Yuyao Feng, Fan Yang, Choufei Wu, Huiming Zhong, Yiting Zhou, Qiming Sun, Liqin Zhang, Wei Liu, Cong Yi
Summary: The DNA damage sensor Mec1 plays an essential role in the DNA damage response pathway and glucose starvation-induced autophagy. It forms puncta and contacts both mitochondria and the phagophore assembly site (PAS) through interactions with the adaptor protein Ggc1 and direct binding with Atg13, respectively. These interactions are mediated by specific protein regions, MBR on Atg13 and ABR on Mec1, and disruption of these regions impairs the recruitment of Mec1 puncta and Atg13 to the PAS, blocking glucose starvation-induced autophagy.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2023)
Review
Microbiology
Muhammad Luqman Nasaruddin, Khaizurin Tajul Arifin
Summary: This scoping review identified a common pathway undertaken by S. cerevisiae under nutritional stress through the application of metabolomics. Changes in cellular nucleoside concentration were observed during nitrogen and glucose starvation, indicating the importance of autophagy in maintaining survival. The practicality of metabolomics in understanding underlying mechanisms for maintaining homeostasis and potential intervention targets against diseases was highlighted.
Article
Multidisciplinary Sciences
Yan Chen, Bin Tsai, Ningning Li, Ning Gao
Summary: The authors report structures of RAC-containing ribosomal complexes, providing insights into the dynamic actions of RAC-Ssb during co-translational folding.
NATURE COMMUNICATIONS
(2022)
Article
Microbiology
Agnese Kokina, Kristel Tanilas, Zane Ozolina, Karlis Pleiko, Karlis Shvirksts, Ilze Vamza, Janis Liepins
Summary: Purine starvation affects cellular morphology, metabolism, and transcriptome in budding yeast, leading to cell cycle arrest, trehalose accumulation, and tolerance to environmental stresses. It also results in significant downregulation of ribosomal biosynthesis genes. The expression of new proteins during purine starvation is critical for cells to attain stress tolerance phenotype.
Article
Biochemistry & Molecular Biology
Eshita Das, Shivcharan Prasad, Ipsita Roy
Summary: Peptidyl prolyl isomerases play a key role in accelerating protein folding, with larger multi-domain proteins having additional functions beyond isomerization. Yeast Fpr1 exhibits characteristics of a general chaperone in the proteostasis network, reducing protein aggregation and improving cell survival. Overexpression of Fpr1 protects cells against thermal shock, suggesting potential therapeutic implications in disease conditions.
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
(2021)
Article
Cell Biology
Madeline G. Rollins, Manidip Shasmal, Nathan Meade, Helen Astar, Peter S. Shen, Derek Walsh
Summary: Poxviruses phosphorylate the ribosomal protein RACK1 in human hosts, altering ribosome structure and translation output to support noncanonical modes of translation and confer resistance to various protein synthesis inhibitors.
Article
Biochemistry & Molecular Biology
Nir Cohen, Amit Kahana, Maya Schuldiner
Summary: Despite our efforts in researching the baker's yeast Saccharomyces cerevisiae, there are still many unknowns in its genome, hindering our understanding of cellular activity and suggesting the presence of unknown processes. However, with advancements in computational methods and the availability of high-quality genomic and structural data, we can now predict and identify candidate enzymes for unannotated proteins in yeast. By using these predictions and experimental validation, we have discovered a new function for an uncharacterized enzyme in the NAD degradation pathway, which has implications in cancer research. This methodology can be applied to other organisms, providing a paradigm for uncovering new enzymatic functions.
JOURNAL OF MOLECULAR BIOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Byung-Sik Shin, Ivaylo P. Ivanov, Joo-Ran Kim, Chune Cao, Terri G. Kinzy, Thomas E. Dever
Summary: Diphthamide (DPH) is a conserved amino acid modification on eukaryotic translation elongation factor eEF2. Loss of DPH impairs translational fidelity, leading to increased rates of ribosomal frameshifting and premature termination at out-of-frame stop codons. The ADP-ribosylation of DPH by bacterial toxins inhibits the binding of eEF2 to elongating ribosomes, further compromising translation accuracy. The costly, yet non-essential, DPH modification has been conserved through evolution to maintain translational fidelity.
NUCLEIC ACIDS RESEARCH
(2023)
Article
Cell Biology
Yongook Lee, Bongkeun Kim, Hae-Soo Jang, Won-Ki Huh
Summary: Macroautophagy/autophagy is a crucial degradation pathway that cells use to maintain homeostasis and survive under stressful conditions. It has been discovered that Atg1-dependent phosphorylation of Vps34 is necessary for robust autophagy activity in yeast. This phosphorylation occurs at multiple serine/threonine residues in the helical domain of Vps34 in complex I and is essential for autophagy activation and cell survival. Furthermore, the localization of Vps34 complex I to the phagophore assembly site (PAS) is responsible for the complex I-specific phosphorylation of Vps34 and affects the dynamics of Atg18 and Atg8 at the PAS.
Review
Biochemistry & Molecular Biology
Ashley J. Ovens, John W. Scott, Christopher G. Langendorf, Bruce E. Kemp, Jonathan S. Oakhill, William J. Smiles
Summary: AMP-activated protein kinase (AMPK) plays a crucial role in adaptive responses to exercise, and its post-translational modifications extensively influence its activity, subcellular localization, nutrient interactions, and protein stability. Areas for further research include novel regulatory modifications of AMPK and improving characterization of these modifications.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Multidisciplinary Sciences
Maximilian Seidel, Natalie Romanov, Agnieszka Obarska-Kosinska, Anja Becker, Nayara Trevisan Doimo de Azevedo, Jan Provaznik, Sankarshana R. Nagaraja, Jonathan J. M. Landry, Vladimir Benes, Martin Beck
Summary: Various cellular quality control mechanisms are involved in maintaining protein homeostasis. In addition to preventing misfolding during translation, ribosome-associated chaperones and importins also play roles in preventing protein aggregation and facilitating nucleocytoplasmic transport. This study suggests that importins can bind to ribosome-associated cargoes in a co-translational manner, including proteins such as ribosomal proteins, chromatin remodelers, and RNA binding proteins that are prone to cytosolic aggregation. The authors also demonstrate that importins act consecutively with other ribosome-associated chaperones, highlighting the interconnectedness of the nuclear import system and nascent chain folding.
NATURE COMMUNICATIONS
(2023)
Article
Biochemistry & Molecular Biology
Alon Chappleboim, Daphna Joseph-Strauss, Omer Gershon, Nir Friedman
Summary: Multiple studies in the last decade have shown that cells maintain a balance of mRNA production and degradation, but the mechanisms behind this balance are still unknown. This study monitored the mRNA profiles in cells after the depletion of Xrn1, the main mRNA exonuclease, and observed an accumulation of mRNA followed by a reduction in transcription and subsequent return to normal levels. The study also found that this transcriptional response is not specific to Xrn1 depletion and occurs earlier when upstream factors in the degradation pathway are disturbed.
NUCLEIC ACIDS RESEARCH
(2022)
Review
Biochemistry & Molecular Biology
Francisco Gutierrez-Santiago, Francisco Navarro
Summary: Ribosomes are vital for protein production, and their biogenesis is regulated by cellular energy status and stress signals. In eukaryotic cells, stress signals and newly-synthesized ribosomes require transcription by RNA polymerases. The Target of Rapamycin pathway in eukaryotes influences RNA polymerase transcription to ensure proper ribosome production. This review focuses on how TOR regulates transcription in Saccharomyces cerevisiae and the coordination of three RNA polymerases.
Article
Hematology
Reiner K. Mailer, Mikel Allende, Marco Heestermans, Michaela Schweizer, Carsten Deppermann, Maike Frye, Giordano Pula, Jacob Odeberg, Mathias Gelderblom, Stefan Rose-John, Albert Sickmann, Stefan Blankenberg, Tobias B. Huber, Christian Kubisch, Coen Maas, Stepan Gambaryan, Dmitri Firsov, Evi X. Stavrou, Lynn M. Butler, Thomas Renne
Summary: Polyphosphate, an inorganic polymer of linear-linked orthophosphate residues, plays a critical role in blood coagulation, with platelet XPR1 identified as a major regulator of polyphosphate metabolism. Pharmacological interference with XPR1 activity led to enhanced platelet-driven coagulation and thrombus formation via the polyphosphate/factor XII pathway. Deletion of Xpr1 in platelets resulted in polyphosphate accumulation, accelerated arterial thrombosis, and increased activated platelet-driven pulmonary embolism in mice. These findings highlight the importance of phosphate homeostasis in thrombosis.
Article
Biotechnology & Applied Microbiology
Sabine Pech, Markus Rehberg, Robert Janke, Dirk Benndorf, Yvonne Genzel, Thilo Muth, Albert Sickmann, Erdmann Rapp, Udo Reichl
Summary: This study investigated the adaptations of animal cells to growth in suspension culture, focusing on the production of viral vaccines. It found that cellular changes on various levels involve alterations in metabolism, enzyme, and proteome. The study also identified four regulatory mechanisms linked to specific proteins in the adaptation of adherent MDCK cells to suspension growth, providing a more holistic view on cellular processes.
APPLIED MICROBIOLOGY AND BIOTECHNOLOGY
(2021)
Article
Biochemical Research Methods
Yassene Mohammed, Pallab Bhowmick, Sarah A. Michaud, Albert Sickmann, Christoph H. Borchers
Summary: The laboratory mouse is a commonly used animal model in biological research, and researchers use it to study various questions such as gene effects and drug metabolism. A knowledgebase called MouseQuaPro has been developed to collect protein concentration data from over 5000 mouse tissues, providing insights into differences between tissues, strains, and sexes.
Article
Genetics & Heredity
Andreas Hentschel, Artur Czech, Ute Muenchberg, Erik Freier, Ulrike Schara-Schmidt, Albert Sickmann, Jens Reimann, Andreas Roos
Summary: Using human skin fibroblasts for proteomic studies revealed a wide variety of proteins related to genetic forms of motoneuron diseases, congenital myasthenic syndromes, neuropathies, and muscle disorders, suggesting the suitability of human skin fibroblasts to study NMD etiology. Proteomic signature of fibroblasts derived from an Allgrove patient showed dysregulation of paradigmatic proteins, which could be confirmed in a muscle biopsy and linked to neurological symptoms. Additionally, proteomic investigation of nuclear protein composition identified protein dysregulations consistent with structural perturbations observed in muscle biopsy, while fluorescence and microscopy techniques indicated altered lipid storage as part of the underlying disease etiology.
ORPHANET JOURNAL OF RARE DISEASES
(2021)
Article
Biochemistry & Molecular Biology
Frederik Braun, Andreas Hentschel, Albert Sickmann, Theodore Marteau, Swantje Hertel, Fabian Foerster, Holger Prokisch, Matias Wagner, Saskia Wortmann, Adela Della Marina, Heike Koelbel, Andreas Roos, Ulrike Schara-Schmidt
Summary: Mutations in the SPATA5 gene are associated with epilepsy, hearing loss, and mental retardation syndrome (EHLMRS). Limited knowledge exists about the associated muscular and molecular pathology. A comprehensive study on an 8-year-old girl with typical EHLMRS clinical presentation revealed muscular pathology abnormalities and dysregulated protein expression.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Review
Biochemistry & Molecular Biology
Jingnan Huang, Pengyu Zhang, Fiorella A. Solari, Albert Sickmann, Angel Garcia, Kerstin Jurk, Johan W. M. Heemskerk
Summary: Platelets, small anucleate blood cells, play crucial roles in haemostasis and thrombosis, regulated by a complex network of signalling pathways. Proteomic techniques contribute to identifying new platelet proteins and post-translational modifications. Research on platelet proteomics provides insight into molecular changes and potential biomarkers for platelet dysfunctions.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Biochemical Research Methods
Bernhardt Sachs, Amol Fatangare, Albert Sickmann, Andreas Glassner
Summary: Drug-induced hypersensitivity reactions can be classified into allergic and non-allergic reactions, with drug allergies further categorized as antibody or T cell-mediated. The lymphocyte transformation test (LTT) is a diagnostic tool for in vitro detection of drug allergy, with the classical LTT measuring T cell proliferation as the read-out parameter. Modifications to the classical LTT in terms of read-out parameters and methods have been proposed over time.
JOURNAL OF IMMUNOLOGICAL METHODS
(2021)
Article
Hematology
Sarah Beck, David Stegner, Stefan Loroch, Ayesha A. Baig, Vanessa Goeb, Cornelia Schumbrutzki, Eva Eilers, Albert Sickmann, Frauke May, Marc W. Nolte, Con Panousis, Bernhard Nieswandt
Summary: This study developed a humanized FXII mouse model by replacing the murine F12 gene with the human gene, tested it in in vitro coagulation assays and in vivo thrombosis models. The hF12(KI) mice were indistinguishable from wild-type mice in all tested assays, except for reduced expression levels of hFXII compared to human plasma. Targeting FXII with the anti-human FXIIa antibody 3F7 increased activated partial thromboplastin time dose-dependently and protected hF12(KI) mice in an arterial thrombosis model without affecting bleeding times.
JOURNAL OF THROMBOSIS AND HAEMOSTASIS
(2021)
Article
Multidisciplinary Sciences
Corvin Walter, Adinarayana Marada, Tamara Suhm, Ralf Ernsberger, Vera Muders, Cansu Kuecuekkoese, Pablo Sanchez-Martin, Zehan Hu, Abhishek Aich, Stefan Loroch, Fiorella Andrea Solari, Daniel Poveda-Huertes, Alexandra Schwierzok, Henrike Pommerening, Stanka Matic, Jan Brix, Albert Sickmann, Claudine Kraft, Joern Dengjel, Sven Dennerlein, Tilman Brummer, F. -Nora Voegtle, Chris Meisinger
Summary: The study shows that DYRK1A phosphorylates TOM70 to promote import of precursor proteins into mitochondria. Inhibition of DYRK1A impairs mitochondrial structure and function, leading to a decrease in metabolite carrier import capacity.
NATURE COMMUNICATIONS
(2021)
Article
Multidisciplinary Sciences
Marco Heestermans, Clement Naudin, Reiner K. Mailer, Sandra Konrath, Kristin Klaetschke, Anne Jamsa, Maike Frye, Carsten Deppermann, Giordano Pula, Piotr Kuta, Manuel A. Friese, Mathias Gelderblom, Albert Sickmann, Roger J. S. Preston, Jerzy-Roch Nofer, Stefan Rose-John, Lynn M. Butler, Ophira Salomon, Evi X. Stavrou, Thomas Renne
Summary: The study reveals the critical role of the Gln317-Ser339 region in FXII protein in blood coagulation and thrombus formation, with the potential for antibody-induced activation of FXII to be used in sensitive monitoring of coagulation factors.
NATURE COMMUNICATIONS
(2021)
Article
Multidisciplinary Sciences
Jingnan Huang, Frauke Swieringa, Fiorella A. Solari, Isabella Provenzale, Luigi Grassi, Ilaria De Simone, Constance C. F. M. J. Baaten, Rachel Cavill, Albert Sickmann, Mattia Frontini, Johan W. M. Heemskerk
Summary: Novel analysis of platelet and megakaryocyte transcriptome revealed high similarity between their transcriptomes, with redistribution of mRNAs upon platelet shedding from megakaryocytes. A prediction model based on protein function, transcript level and (peri)nuclear localization estimated the achievable proteome of about 10 k proteins, with identification of additional proteins related to thrombosis and platelet disorders. This genome-wide platelet transcriptome provides a valuable resource for studying the roles of unknown platelet proteins in health and disease.
SCIENTIFIC REPORTS
(2021)
Article
Biochemistry & Molecular Biology
Constanze Schanbacher, Michael Bieber, Yvonne Reinders, Deya Cherpokova, Christina Teichert, Bernhard Nieswandt, Albert Sickmann, Christoph Kleinschnitz, Friederike Langhauser, Kristina Lorenz
Summary: The activation or inhibition of the ERK1/2 signaling cascade has a significant impact on the outcome of ischemic stroke. This study found that overexpression of wild-type ERK2 worsened the infarct volume and neurological deficits, as well as increased blood-brain barrier leakage, inflammation, and apoptotic neurons. In contrast, inhibition of the Raf/MEK/ERK1/2 cascade provided protection against ischemic damage, primarily through anti-inflammatory signaling.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Oncology
Andrea Gangfuss, Artur Czech, Andreas Hentschel, Ute Munchberg, Rita Horvath, Ana Topf, Emily O'Heir, Hanns Lochmuller, Florian Stehling, Cordula Kiewert, Albert Sickmann, Alma Kuechler, Frank J. Kaiser, Heike Kolbel, Jon Christiansen, Ulrike Schara-Schmidt, Andreas Roos
Summary: Recessive variants in WASHC4 are associated with intellectual disability, poor language skills, and other complications. While studies in a zebrafish model suggest that WASHC4 knockdown may affect skeletal muscles, the involvement of skeletal muscles in patients has not been reported, indicating a need for further research.
JOURNAL OF PATHOLOGY
(2022)
Article
Genetics & Heredity
Annabelle Arlt, Nicolai Kohlschmidt, Andreas Hentschel, Enrika Bartels, Claudia Gross, Ana Toepf, Pinar Edem, Nora Szabo, Albert Sickmann, Nancy Meyer, Ulrike Schara-Schmidt, Jarred Lau, Hanns Lochmueller, Rita Horvath, Yavuz Oktay, Andreas Roos, Semra Hiz
Summary: Goltz syndrome is an X-linked disorder characterized by skin pigmentation, ocular and skeletal malformations, and male in utero lethality. Neurological deficits in GS are rare, with less severe phenotypes potentially caused by non-mosaic survival in males or less pathogenic mutations. Additional molecular genetics and functional work-up is needed to understand the rare variants.
ORPHANET JOURNAL OF RARE DISEASES
(2022)
Article
Biochemistry & Molecular Biology
Julia Hesse, Mona K. Rosse, Bodo Steckel, Bernhard Blank-Landeshammer, Svenja Idel, Yvonne Reinders, Albert Sickmann, Norbert Straeter, Juergen Schrader
Summary: CD73-derived adenosine plays a major role in damage-induced tissue responses by inhibiting inflammation. This study suggests that human CD73 enzymatic activity is regulated by mono-ADP-ribosylation, which can profoundly modulate its adenosine-generating activity.
PURINERGIC SIGNALLING
(2022)