Article
Biotechnology & Applied Microbiology
Diana Chinyere Anyaogu, Anders Holmgaard Hansen, Jakob Blaesbjerg Hoof, Natalia Majewska, Fabiano Jares Contesini, Jackson T. Paul, Kristian Fog Nielsen, Timothy John Hobley, Shuang Yang, Hui Zhang, Michael Betenbaugh, Uffe Hasbro Mortensen
Summary: Filamentous fungi have the potential to secrete proteins efficiently for low-cost production, but the differences in N-glycosylation compared to humans pose a significant barrier for producing therapeutic proteins with appropriate glycosylation. Reprogramming the glycosylation pathway of fungi, such as Aspergilli, can help in decorating proteins with glycans that are more suitable for human acceptance. Further strain optimization may be necessary in order to achieve the desired glycan structures.
METABOLIC ENGINEERING
(2021)
Article
Oncology
Anthony B. B. El-Khoueiry, James Clarke, Tobias Neff, Tim Crossman, Nirav Ratia, Chetan Rathi, Paul Noto, Aarti Tarkar, Ignacio Garrido-Laguna, Emiliano Calvo, Jordi Rodon, Ben Tran, Peter J. J. O'Dwyer, Adam Cuker, Albiruni R. Abdul R. Razak
Summary: GSK3368715, a reversible inhibitor of type I protein methyltransferases, showed anticancer activity in preclinical studies. This Phase 1 study evaluated its safety, pharmacokinetics, pharmacodynamics, and preliminary efficacy in patients with advanced solid tumors. However, due to a higher-than-expected incidence of thromboembolic events, the study was terminated.
BRITISH JOURNAL OF CANCER
(2023)
Article
Chemistry, Medicinal
Lucas Lorenzon, Jose C. Quilles Jr, Gustavo Daniel Campagnaro, Lissur Azevedo Orsine, Leticia Almeida, Flavio Veras, Rubens Daniel Miserani Magalhaes, Juliana Alcoforado Diniz, Tiago Rodrigues Ferreira, Angela Kaysel Cruz
Summary: In trypanosomatids, RNA-binding proteins (RBPs) play a crucial role in gene expression regulation through the posttranscriptional modification by protein arginine methyltransferases (PRMTs). This study functionally characterized the predicted PRMTs in Leishmania braziliensis and revealed the variation of R-methylation profiles among Leishmania species and different lifecycle stages. The results suggest the existence of a PRMT-interacting protein network and the importance of arginine methylation in parasite-host cell interactions.
ACS INFECTIOUS DISEASES
(2022)
Article
Biochemistry & Molecular Biology
Kun Ho Kim, Zhihao Jia, Madigan Snyder, Jingjuan Chen, Jiamin Qiu, Stephanie N. Oprescu, Xiyue Chen, Sabriya A. Syed, Feng Yue, Bruno T. Roseguini, Anthony N. Imbalzano, Changdeng Hu, Shihuan Kuang
Summary: Protein Arginine Methyl Transferase 5 (PRMT5) plays a crucial role in skeletal muscle by linking lipid metabolism to contractile function. Deletion of PRMT5 in skeletal muscle leads to reduced muscle mass, oxidative capacity, force production, and exercise performance. This deficiency is associated with defects in lipid biosynthesis, accelerated degradation, and reduced levels of key regulators such as SREBP1a and ATGL. Restoring the balance of these regulators can normalize muscle mass and function.
Article
Oncology
Shuangjie Liu, Zhuonan Liu, Chiyuan Piao, Zhe Zhang, Chuize Kong, Lei Yin, Xi Liu
Summary: The study reveals PRMT5 as a therapeutic target for bladder cancer and identifies FKA, extracted from the kava plant, as an inhibitor of PRMT5 for the treatment of bladder cancer.
JOURNAL OF EXPERIMENTAL & CLINICAL CANCER RESEARCH
(2022)
Article
Microbiology
Valentin Wernet, Satur Herrero, Reinhard Fischer
Summary: The study reveals the differences in growth mechanisms between fast-growing fungi and slow-growing fungi, indicating a tradeoff between hyphal plasticity and growth speed.
Article
Biotechnology & Applied Microbiology
Keiko Takagi, Akari Kikkawa, Ryo Iwama, Ryouichi Fukuda, Hiroyuki Horiuchi
Summary: Phosphatidylserine decarboxylases (PSDs) play a crucial role in maintaining phosphatidylethanolamine (PE) levels in fungi, with type II PSDs being unique to fungi and plants and important for fungal growth and morphogenesis. Deletion of psdB in Aspergillus nidulans resulted in severe growth defects, reduced conidiation efficiency, and abnormal conidiophore structures, highlighting the significant role of type II PSDs in phospholipid homeostasis and fungal development.
JOURNAL OF BIOSCIENCE AND BIOENGINEERING
(2021)
Article
Biochemistry & Molecular Biology
Qin Wu, David Y. Nie, Wail Ba-alawi, YiShuai Ji, ZiWen Zhang, Jennifer Cruickshank, Jillian Haight, Felipe E. Ciamponi, Jocelyn Chen, Shili Duan, Yudao Shen, Jing Liu, Sajid A. Marhon, Parinaz Mehdipour, Magdalena M. Szewczyk, Nergiz Dogan-Artun, WenJun Chen, Lan Xin Zhang, Genevieve Deblois, Panagiotis Prinos, Katlin B. Massirer, Dalia Barsyte-Lovejoy, Jian Jin, Daniel D. De Carvalho, Benjamin Haibe-Kains, XiaoJia Wang, David W. Cescon, Mathieu Lupien, Cheryl H. Arrowsmith
Summary: This study identified an inhibitor called MS023 that has antitumor growth activity in triple-negative breast cancer (TNBC). Activation of interferon responses was found to be a functional biomarker and determinant of response in TNBC cell lines and human-derived organoids. Inhibition of type I PRMT triggers an interferon response through the antiviral defense pathway.
NATURE CHEMICAL BIOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Anezia Kourkoulou, Iliana Zantza, Konstantina Foti, Emmanuel Mikros, George Diallinas
Summary: Members of the NAT family are symporters specific for the uptake of purines, pyrimidines, or L-ascorbic acid. This study reveals the roles of partially conserved residues in determining the specificity of the UapA transporter. Results show that UapA specificity is genetically modifiable, allowing for speculation on the flexible mechanism of transport.
JOURNAL OF MOLECULAR BIOLOGY
(2021)
Article
Chemistry, Analytical
Zhen Liu, Keyun Wang, Mingliang Ye
Summary: In order to understand the function of protein arginine methyltransferases(PRMTs), it is crucial to identify their substrate proteins. However, this is challenging due to the dominance of stable and strong interacting proteins over weak and transient substrate proteins. In this study, a novel photoreactive probe-based strategy was developed to identify the substrate proteins of methyltransferases, specifically PRMT1. This strategy effectively distinguished substrate proteins from other interacting proteins and allowed the identification of highly confident substrate proteins. Importantly, it was discovered that hypomethylation of proteins is a prerequisite for efficient capturing of substrate proteins. This study describes the development of a robust chemical proteomic tool for profiling transient substrates and has broad biomedical applications.
ANALYTICAL CHEMISTRY
(2023)
Article
Pharmacology & Pharmacy
Ayad A. Al-Hamashi, Dongxing Chen, Youchao Deng, Guangping Dong, Rong Huang
Summary: This study reported the design and synthesis of bisubstrate analogues for PRMTs, with compound AH237 showing potent and selective inhibition towards PRMT4 and PRMT5. Computational studies provided insights into the high potency and selectivity of AH237, offering a valuable strategy for developing inhibitors for PRMTs in the future.
ACTA PHARMACEUTICA SINICA B
(2021)
Article
Endocrinology & Metabolism
Seri Choi, Dahee Choi, Yun-Kyung Lee, Seung Hyun Ahn, Je Kyung Seong, Sung Wook Chi, Tae Jung Oh, Sung Hee Choi, Seung-Hoi Koo
Summary: PRMT1 plays a crucial role in maintaining metabolic balance in adipose tissues, with its depletion leading to increased lipid catabolism and adverse effects in conditions of high-fat diet or obesity, such as promotion of adipose tissue inflammation and ectopic accumulation of triglycerides.
Review
Endocrinology & Metabolism
Huimei Wei, Peng Huo, Shun Liu, Hua Huang, Shun Zhang
Summary: PCOS is a lifelong disorder affecting a significant number of women and associated with increased risk of various diseases. Posttranslational modifications play a crucial role in PCOS development, and understanding their roles and mechanisms can provide insights for future research and treatment.
FRONTIERS IN ENDOCRINOLOGY
(2022)
Review
Medicine, Research & Experimental
Jiaoyang Ning, Liu Chen, Gang Xiao, Yu Zeng, Wen Shi, Guilong Tanzhu, Rongrong Zhou
Summary: PRMTs are involved in the prognosis and metastasis of tumors, and their regulation of molecular mechanisms affects tumor metastasis. Inhibiting arginine methylation can reduce tumor metastasis, and this field holds promise for clinical application.
BIOMEDICINE & PHARMACOTHERAPY
(2023)
Article
Microbiology
Xiaohui Ju, Yanying Yu, Wenlin Ren, Lin Dong, Xianbin Meng, Haiteng Deng, Yuchen Nan, Qiang Ding
Summary: This study systematically analyzed the host factors in HEV replication complex using ORF1 trans-complementation system and HEV replicon. The PRMT5/WDR77 complex was found to have an inhibitory role in HEV infection among different HEV strains, but not in HCV and SARS-CoV-2 infection. The complex methylates the 458th arginine in HEV ORF1, which is responsible for HEV replication. The findings provide insights into HEV replication and viral-host interaction, and inform antiviral strategies against HEV infection.
Article
Multidisciplinary Sciences
Ingo Bauer, Angelo Pidroni, Ozgur Bayram, Gerald Brosch, Stefan Graessle
JOVE-JOURNAL OF VISUALIZED EXPERIMENTS
(2019)
Article
Microbiology
Ingo Bauer, Silke Gross, Petra Merschak, Leopold Kremser, Betim Karahoda, Ozlem Sarikaya Bayram, Beate Abt, Ulrike Binder, Fabio Gsaller, Herbert Lindner, Ozgur Bayram, Gerald Brosch, Stefan Graessle
FRONTIERS IN MICROBIOLOGY
(2020)
Article
Microbiology
Lukas Birstonas, Alex Dallemulle, Manuel S. Lopez-Berges, Ilse D. Jacobsen, Martin Offterdinger, Beate Abt, Maria Strassburger, Ingo Bauer, Oliver Schmidt, Bettina Sarg, Herbert Lindner, Hubertus Haas, Fabio Gsaller
Article
Genetics & Heredity
Anna-Maria Dietl, Ulrike Binder, Ingo Bauer, Yana Shadkchan, Nir Osherov, Hubertus Haas
Review
Genetics & Heredity
Ingo Bauer, Stefan Graessle
Summary: As the number of immunocompromised patients grows, there is a need for efficient therapy strategies against invasive fungal infections; conventional antifungal treatments are increasingly limited by drug resistance, necessitating the development of new therapies; there is immense potential in utilizing natural products from fungi for medical and industrial applications, with the acetylation status of regulatory proteins playing a significant role.
Article
Cell Biology
Ines Schoberleitner, Ingo Bauer, Anming Huang, Evgeniya N. Andreyeva, Johanna Sebald, Katharina Pascher, Dietmar Rieder, Melanie Brunner, Valerie Podhraski, Gregor Oemer, Daniel Cazarez-Garcia, Leila Rieder, Markus A. Keller, Robert Winkler, Dmitry Fyodorov, Alexandra Lusser
Summary: CHD1 is essential for assembling H3.3 chromatin in adult cells, particularly in the brain, playing a crucial role in regulating organismal health and longevity.
Article
Neurosciences
Ines Schoberleitner, Birte Mertens, Ingo Bauer, Alexandra Lusser
Summary: The ATP-dependent chromatin remodeling factor CHD1 plays a crucial role in the incorporation of the histone variant H3.3 in the fly brain, affecting sensory perception genes and leading to defects in olfactory and gustatory response behavior. Additionally, Chd1-mutant flies exhibit shortened lifespan and indications of premature functional aging, including impaired negative geotaxis and exploratory walking. Neuronal re-expression of Chd1 rescues the exploratory walking phenotype but not the olfactory defects.
FRONTIERS IN MOLECULAR NEUROSCIENCE
(2022)
Article
Biochemistry & Molecular Biology
Betim Karahoda, Lakhansing Pardeshi, Mevlut Ulas, Zhiqiang Dong, Niranjan Shirgaonkar, Shuhui Guo, Fang Wang, Kaeling Tan, Ozlem Sarikaya-Bayram, Ingo Bauer, Paul Dowling, Alastair B. Fleming, Brandon T. Pfannenstiel, Dianiris Luciano-Rosario, Harald Berger, Stefan Graessle, Mohamed M. Alhussain, Joseph Strauss, Nancy P. Keller, Koon Ho Wong, Ozgur Bayram
Summary: This study describes a chromatin binding complex KERS in the fungus Aspergillus nidulans, consisting of H3K4 histone demethylase KdmB, cohesin acetyltransferase EcoA, histone deacetylase RpdA, and histone reader/E3 ligase protein SntB. The KERS complex exerts promoter-specific transcriptional effects at active core promoters.
NUCLEIC ACIDS RESEARCH
(2022)
Article
Microbiology
Ingo Bauer, Beate Abt, Annie Yap, Bernd Leuchtle, Hubertus Haas
Summary: In this study, CGQ was used to monitor biomass of A. fumigatus in liquid shake cultures, showing a strong correlation with classical dry-weight determination and revealing differences in growth patterns of different strains under different growth conditions.
Article
Chemistry, Medicinal
Sarah Moreno, Magdalena Fickl, Ingo Bauer, Melanie Brunner, Anna Razkova, Dietmar Rieder, Isabel Delazer, Ronald Micura, Alexandra Lusser
Summary: This study investigated the potential of 6-thioguanosine monophosphate (6sGMP) prodrugs to overcome resistance to 6-thioguanine. The researchers successfully developed synthetic routes for various 6sGMP prodrugs and found that certain derivatives were effective in cells resistant to thiopurines. The study also demonstrated the intracellular conversion of 6sGMP prodrugs into bioactive compounds. TUC-seq DUAL was suggested as a simple and fast method to measure the success of thiopurine therapy.
JOURNAL OF MEDICINAL CHEMISTRY
(2022)
Article
Immunology
Thomas Orasch, Anna-Maria Dietl, Yana Shadkchan, Ulrike Binder, Ingo Bauer, Cornelia Lass-Floerl, Nir Osherov, Hubertus Haas