Review
Cell Biology
Tatyana Bodrug, Kaeli A. Welsh, Megan Hinkle, Michael J. Emanuele, Nicholas G. Brown
Summary: The ubiquitin-proteasome system plays a crucial role in cell cycle regulation, neurobiology, and chromatin control. Recent studies have revealed new mechanisms of APC/C activity and its involvement in broader signaling pathways.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2021)
Review
Plant Sciences
Marina de Lyra Soriano Saleme, Ingrid Rocha Andrade, Nubia Barbosa Eloy
Summary: Most eukaryotic species propagate through sexual reproduction involving male and female gametes. In flowering plants, this process begins with DNA replication and chromosome segregation, followed by mitotic divisions to form male and female gametophytes. Precise regulation of gametogenesis progression is essential for successful meiotic cell division and sexual differentiation in plant species.
FRONTIERS IN PLANT SCIENCE
(2021)
Review
Immunology
Xiaoyan Xia, Anchun Cheng, Mingshu Wang, Xumin Ou, Di Sun, Sai Mao, Juan Huang, Qiao Yang, Ying Wu, Shun Chen, Shaqiu Zhang, Dekang Zhu, Renyong Jia, Mafeng Liu, Xin-Xin Zhao, Qun Gao, Bin Tian
Summary: Viroporins play a crucial role in the viral life cycle by altering host cell functions and evading immune responses, ensuring the survival of the virus. Therefore, viroporins have become an important target for antiviral therapies.
FRONTIERS IN IMMUNOLOGY
(2022)
Review
Cell Biology
Alex Willems, Lieven De Veylder
Summary: The review focuses on the plant APC/C complex, discussing its importance in plant development and its association with different developmental processes. The interactions between plant-specific APC/C activator subunits and other subunits are also described. Finally, a comprehensive list of confirmed and suspected plant APC/C target proteins is provided, offering opportunities to manipulate APC/C activity for increased crop yield and improved resilience to climate change.
ANNUAL REVIEW OF CELL AND DEVELOPMENTAL BIOLOGY
(2022)
Article
Plant Sciences
Rodrigo Porto Schwedersky, Marina de Lyra Soriano Saleme, Ingrid Andrade Rocha, Patricia da Fonseca Montessoro, Adriana Silva Hemerly, Nubia Barbosa Eloy, Paulo Cavalcanti Gomes Ferreira
Summary: The study reveals the crucial role of APC11 in early plant development, mediating overall plant growth by regulating APC/C activity.
FRONTIERS IN PLANT SCIENCE
(2021)
Article
Multidisciplinary Sciences
Eyashin Ali, Manash Jyoti Kalita, Simanta Kalita, Jayasree Talukdar, Ankur Jyoti Deka, Jasmin Sultana, Bikash Narayan Choudhury, Munindra Narayan Baruah, Sahana Bhattacharjee, Subhash Medhi
Summary: Esophageal squamous cell carcinoma (ESCC) is a prevalent type of esophageal cancer worldwide with a poor prognosis. Dysregulation of anaphase promoting complex/cyclosome (APC/C) activation due to altered expression of APC molecules may contribute to the development of ESCC. The study analyzed the expression of APC/C complex subunits and found significant upregulation of APC7 and APC3, which suggested their role in uncontrolled cell proliferation in ESCC. Additionally, lifestyle factors and their association with APC expression were also studied.
Article
Evolutionary Biology
Samuel H. A. von der Dunk, Berend Snel, Paulien Hogeweg
Summary: The interplay between adaptive and neutral processes in genome expansion and cellular complexity evolution is not yet fully understood. This study investigates the regulatory repertoire of cells and its relationship with genome size in a computational model. Results show that adaptation leads to the expansion of the regulatory repertoire and improved cell-cycle behavior, but at the cost of a large genome. Different evolutionary trajectories resulted in distinct eco-evolutionary strategies, highlighting the role of contingency in a system under strong selective forces.
GENOME BIOLOGY AND EVOLUTION
(2022)
Article
Biochemistry & Molecular Biology
Siyu Huang, Pin Wan, Shanyu Huang, Siyu Liu, Qi Xiang, Ge Yang, Muhammad Adnan Shereen, Pan Pan, Jun Wang, Weiyong Liu, Kailang Wu, Jianguo Wu
Summary: The study reveals that APC10 is a critical mediator in regulating NLRP3 inflammasome activation during the cell cycle, acting as a switch by interacting with NLRP3 to either promote or repress inflammatory responses.
Review
Microbiology
Boris Bogdanow, Quang Vinh Phan, Luder Wiebusch
Summary: Cytomegaloviruses induce significant changes in cell cycle regulation to enable replication of their DNA genomes. They establish a unique cell cycle arrest at the G(1)/S transition, while activating S phase-specific gene expression and nucleotide metabolism. Despite similarities in cell cycle regulation between human and murine CMVs, there are considerable differences in viral cell cycle effectors and mechanisms of action.
Article
Virology
Jeremy A. Ferreira Barbosa, Samantha Sparapani, Jonathan Boulais, Robert Lodge, Eric A. Cohen
Summary: The HIV-1 Vpr protein interacts with the APC/C complex to mediate the degradation of APC1, a critical component of the complex. It was found that targeting APC/C by Vpr does not impact known Vpr activities, suggesting that the interplay between Vpr and APC/C may govern other aspects of HIV-1 pathogenesis.
JOURNAL OF VIROLOGY
(2021)
Review
Biochemistry & Molecular Biology
Marios G. Koliopoulos, Claudio Alfieri
Summary: The cell cycle is a crucial biological process where CDKs act as an oscillator to regulate orderly progression through different phases. Cryo-electron microscopy has revolutionized our understanding of the molecular function and dynamics of key players in the cell cycle.
Review
Virology
Meilin Li, Dingkun Peng, Hongwei Cao, Xiaoke Yang, Su Li, Hua-Ji Qiu, Lian-Feng Li
Summary: Viruses depend on their hosts to infect, replicate, and generate new viruses. They have evolved strategies to hijack and control the host cytoskeleton, which is involved in viral life cycle and cell-to-cell transmission. The host also mounts cytoskeleton-mediated antiviral immune responses. This review summarizes the functions of prominent viruses in manipulating the cytoskeleton and the related antiviral responses, aiming to provide insights for the development of novel antivirals targeting the cytoskeleton.
Review
Biochemistry & Molecular Biology
Sanghati Roy Chowdhury, Tirthankar Koley, Mandeep Singh, Abdul Samath Ethayathulla, Punit Kaur
Summary: The complex molecular interactions leading to the oncogenic pathway are a result of cell cycle modification controlled by cell cycle regulatory proteins. Tumor suppressor and cell cycle regulatory proteins work together to maintain a healthy cellular environment. Heat shock proteins/chaperones, including Hsp90, play an important role in stabilizing tumor suppressors and cell cycle regulator proteins. Recent studies have shown that Hsp90 stabilizes mutant p53 and Fzr, which are crucial in regulating the cell cycle and preventing oncogenic processes. Dysfunction of this cellular process can lead to cancer development. Current drug trials targeting Hsp90 are discussed.
BIOCHIMICA ET BIOPHYSICA ACTA-REVIEWS ON CANCER
(2023)
Article
Biochemistry & Molecular Biology
Puja Chakraborty, Ratnadip Paul, Abhishek Chowdhury, Nayonika Mukherjee, Somsubhra Nath, Susanta Roychoudhury
Summary: This study investigates the role of histone ubiquitylation in transcription regulation, particularly the mono-ubiquitylation of histone 2B by RING finger motif-containing ubiquitin ligases. The study shows that the anaphase-promoting complex/cyclosome (APC/C), along with its adapter protein Cdc20, catalyses the mono-ubiquitylation of Lysine-120 on the UBCH10 promoter. The study also uncovers a cell-cycle-specific pattern of this modification and suggests a crosstalk between acetylation and ubiquitylation in UBCH10 trans-regulation.
Review
Cell Biology
Nicole L. Diggins, Meaghan H. Hancock
Summary: Viruses use various mechanisms to overcome barriers to infection in host cells. One such mechanism is the use of virally-encoded microRNAs (miRNAs) to regulate host gene expression for the benefit of the virus. Despite little sequence homology, different viruses target common cellular pathways such as apoptosis, immune evasion, cell growth, and differentiation. This article highlights the importance of viral miRNAs in lytic and latent infections by targeting these common cellular processes and provides insights into their mimicry of host cell miRNAs and regulation of host miRNA expression.
SEMINARS IN CELL & DEVELOPMENTAL BIOLOGY
(2023)
Review
Virology
Yousef M. O. Alhammad, Anthony R. Fehr
Article
Biochemistry & Molecular Biology
Collin D. Heer, Daniel J. Sanderson, Lynden S. Voth, Yousef M. O. Alhammad, Mark S. Schmidt, Samuel A. J. Trammell, Stanley Perlman, Michael S. Cohen, Anthony R. Fehr, Charles Brenner
JOURNAL OF BIOLOGICAL CHEMISTRY
(2020)
Article
Virology
Lynden S. Voth, Joseph J. O'Connor, Catherine M. Kerr, Ethan Doerger, Nancy Schwarting, Parker Sperstad, David K. Johnson, Anthony R. Fehr
Summary: The macrodomain Mac1 within nonstructural protein 3 of coronaviruses has been identified as essential for viral replication, with targeted mutations revealing multiple functions that contribute to the replication of the model CoV MHV. These findings suggest that Mac1 may be a potential target for anti-CoV therapeutics.
JOURNAL OF VIROLOGY
(2021)
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
Morgan Dasovich, Junlin Zhuo, Jack A. Goodman, Ajit Thomas, Robert Lyle McPherson, Aravinth Kumar Jayabalan, Veronica F. Busa, Shang-Jung Cheng, Brennan A. Murphy, Karli R. Redinger, Yousef M. O. Alhammad, Anthony R. Fehr, Takashi Tsukamoto, Barbara S. Slusher, Jurgen Bosch, Huijun Wei, Anthony K. L. Leung
Summary: Viral macrodomains are crucial for virus replication and pathogenesis, making them a promising target for antiviral therapy. Dasatinib has been identified as a potential ADP-ribosylhydrolase inhibitor, showing effectiveness against SARS-CoV-2 and MERS-CoV, but not affecting the closest human homologue MacroD2. This study demonstrates the feasibility of identifying selective inhibitors based on ADP-ribosylhydrolase activity and provides a potential avenue for developing better macrodomain inhibitors as antiviral therapies for SARS-CoV-2 and other viral threats.
ACS CHEMICAL BIOLOGY
(2022)
Article
Microbiology
Anthony K. L. Leung, Diane E. Griffin, Juergen Bosch, Anthony R. Fehr
Summary: Emerging and re-emerging viral diseases pose continuous threats to public health. Developing a diverse portfolio of antiviral agents is crucial for effective control. The macrodomain, a drug target critical for the replication and pathogenesis of alphaviruses and coronaviruses, has the potential to block virus replication and restore the host's protective interferon response. Macrodomain inhibitors, with their well-defined binding pocket, offer an attractive target for developing direct acting antivirals and complementing current approaches in combating COVID-19 and future viral threats.
Article
Multidisciplinary Sciences
Courtney E. Comar, Clayton J. Otter, Jessica Pfannenstiel, Ethan Doerger, David M. Renner, Li Hui Tan, Stanley Perlman, Noam A. Cohen, Anthony R. Fehr, Susan R. Weiss
Summary: MERS-CoV optimizes its replication by suppressing early innate immune pathways, including interferon production and signaling, through the actions of endoribonuclease (EndoU) and accessory proteins NS4a and NS4b.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Article
Pharmacology & Pharmacy
Anu Roy, Yousef M. Alhammad, Peter McDonald, David K. Johnson, Junlin Zhuo, Sarah Wazir, Dana Ferraris, Lari Lehtio, Anthony K. L. Leung, Anthony R. Fehr
Summary: This study focuses on screening for potential inhibitors of the SARS-CoV-2 conserved macrodomain (Mac1). Five compounds from three chemotypes were identified, which show inhibitory effects on Mac1-ADP-ribose binding, ADP-ribosylhydrolase activity, and direct Mac1 binding, making them strong candidates for the development of highly effective Mac1 inhibitors.
ANTIVIRAL RESEARCH
(2022)
Article
Biochemistry & Molecular Biology
Lavinia M. Sherrill, Elva E. Joya, AnnMarie Walker, Anuradha Roy, Yousef M. Alhammad, Moriama Atobatele, Sarah Wazir, George Abbas, Patrick Keane, Junlin Zhuo, Anthony K. L. Leung, David K. Johnson, Lari Lehtio, Anthony R. Fehr, Dana Ferraris
Summary: A series of amino acid based compounds were designed and synthesized to investigate their inhibitory activity against the SARS-CoV-2 nsp3 macrodomain. Compound 15c was identified as a low-micromolar inhibitor and demonstrated selectivity for coronavirus macrodomains.
BIOORGANIC & MEDICINAL CHEMISTRY
(2022)
Article
Microbiology
Srivatsan Parthasarathy, Anthony R. Fehr
Summary: The translation discusses the impact of posttranslational modifications (PTMs) on protein functions, focusing on the role of ADP-ribosylation. Specifically, it highlights the importance of PARP14, a MARylating enzyme, in anti-inflammatory and antiviral responses, while also emphasizing the need for further studies to elucidate its specific roles and mechanisms during viral infections.
Article
Microbiology
Cindy Y. Ly, Jessica Pfannenstiel, Anil Pant, Zhilong Yang, Anthony R. Fehr, Maxim S. Rodzkin, David J. Davido
Summary: In this study, aurora kinase inhibitors were found to significantly reduce gene expression and viral replication of herpes simplex virus 1 (HSV-1). Furthermore, these inhibitors also showed inhibitory effects on the replication of other RNA and DNA viruses. These findings suggest a novel role for aurora kinases in the replication of diverse viruses.
MICROBIOLOGY SPECTRUM
(2023)
Article
Virology
Catherine M. Kerr, Srivatsan Parthasarathy, Nancy Schwarting, Joseph J. O'Connor, Jessica J. Pfannenstiel, Emily Giri, Sunil More, Robin C. Orozco, Anthony R. Fehr
Summary: PARP12 is an important mediator of the antiviral response to coronaviruses, but additional PARPs or innate immune factors contribute to virus attenuation in mice. PARP12 knockout increases Mac1 mutant virus replication and liver pathology in mice.
JOURNAL OF VIROLOGY
(2023)
Article
Microbiology
Joseph J. O'Connor, Lynden Voth, Jeremiah Athmer, Nicholas M. George, Christopher M. Connelly, Anthony R. Fehr
Summary: Testing two commercially available blood collection tube blood-stabilization reagents, cfDNA and CytoChex, it was found that they can rapidly inactivate coronaviruses and effectively preserve viral RNA stability for a certain period of time.
Review
Microbiology
Joseph J. O'Connor, Dana Ferraris, Anthony R. Fehr
Summary: This article summarizes the progress in the search for inhibitors of the SARS-CoV-2 Mac1 protein. Various unique chemical inhibitors have been successfully created using high-throughput screening and chemical modifications.
Article
Virology
Yousef M. O. Alhammad, Maithri M. Kashipathy, Anuradha Roy, Jean-Philippe Gagne, Peter McDonald, Philip Gao, Louis Nonfoux, Kevin P. Battaile, David K. Johnson, Erik D. Holmstrom, Guy G. Poirier, Scott Lovell, Anthony R. Fehr
Summary: The Mac1 proteins in SARS-CoV-2 and other CoVs are MAR-hydrolases with similar functions, suggesting compounds targeting these proteins may have broad anti-CoV activity. Understanding the biochemistry and enzyme activity of these proteins is critical for developing novel therapeutic strategies against COVID-19.
JOURNAL OF VIROLOGY
(2021)