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
Multidisciplinary Sciences
Stephanie L. Sarbanes, Vincent A. Blomen, Eric Lam, Soren Heissel, Joseph M. Luna, Thijn R. Brummelkamp, Erik Falck-Pedersen, H-Heinrich Hoffmann, Charles M. Rice
Summary: The journey of DNA viruses from the plasma membrane to the nuclear pore is crucial for viral replication, with MIB1 identified as a critical host factor for Adenovirus infectivity. MIB1's ubiquitination activity is essential for promoting AdV infection by potentially degrading negative regulators. This study highlights a new way that viruses exploit host cell machinery for replication, suggesting a potential target for therapeutic interventions against AdV infection.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Editorial Material
Biochemistry & Molecular Biology
Laura A. Hehl, Brenda A. Schulman
Summary: Tsai et al.1 and Mark et al.2 show that the E3 ligase UBR5 mediates broad regulation by selectively targeting agonist-bound nuclear hormone receptors, MYC, and other transcriptional regulators not incorporated into active gene expression complexes.
Editorial Material
Biochemistry & Molecular Biology
Yuan Xie, Minglei Zhao
Summary: Proper regulation of protein degradation is crucial for cell physiology. In the recent issue of Cell, Baek et al. revealed the assembly and disassembly mechanism of a widely present ubiquitin ligase class called CRL, through a key regulatory protein, CAND1.
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
Virology
Drayson Graves, Nikolas Akkerman, Scott Bachus, Peter Pelka
Summary: In this study, it was observed that 293 cells were not able to fully complement the late E1A transcripts, leading to growth defects in E1-deleted adenoviruses. This is likely due to splicing differences in E1A RNA between cells and infecting viruses. Complementation of late E1A mRNAs in 293 cells improved viral growth, highlighting the importance of protein complementation in virus production for applications such as vaccine development and gene therapy.
JOURNAL OF VIROLOGY
(2021)
Article
Biochemistry & Molecular Biology
Iga Dalidowska, Olga Gazi, Dorota Sulejczak, Maciej Przybylski, Pawel Bieganowski
Summary: The research showed that the Hsp90 inhibitor 17-AAG effectively reduces the replication rate of human adenovirus 5 and inhibits its transcription of early and late genes, viral DNA replication, and protein expression. Additionally, 17-AAG decreases the level of newly synthesized E1A protein, potentially explaining its anti-adenoviral activity by reducing E1A levels.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Editorial Material
Pharmacology & Pharmacy
Asad M. Taherbhoy, Danette L. Daniels
Summary: This article introduces targeted protein degradation (TPD) and proposes multiple strategies using UBR5 as an E3 ligase to drive degradation of key transcriptional targets implicated in disease.
TRENDS IN PHARMACOLOGICAL SCIENCES
(2023)
Article
Biochemistry & Molecular Biology
Yasunori Akaike, Yuki Nakane, Taku Chibazakura
Summary: The adenoviral protein E1A, particularly the 13S variant, plays a crucial role in enhancing CDK2 activity and promoting G2/M-phase arrest. The CR1, CR2, and CR3 domains of E1A contribute to binding to the Cyclin A-CDK2 complex and activation of CDK2.
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
(2021)
Article
Multidisciplinary Sciences
Christina Priest, Rohith T. Nagari, Lara Bideyan, Stephen D. Lee, Alexander Nguyen, Xu Xiao, Peter Tontonoz
Summary: The study illustrates the role of BRAP in modulating the hepatic Hippo pathway by regulating MST2, impacting liver cell morphology and turnover. Loss of BRAP leads to significant morphological changes in the liver, increased hepatocyte proliferation, cell death, and inflammation. The altered Hippo pathway signaling in Brap knockout mice affects liver lipid accumulation in dietary models of obesity, highlighting its relevance to human liver disease.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Article
Medicine, Research & Experimental
Zongang Liu, Mengnan Zhao, Xizi Jiang, Yao Zhang, Suning Zhang, Yitong Xu, Hongjiu Ren, Hongbo Su, Huanxi Wang, Xueshan Qiu
Summary: This study elucidates the role of KLHL17 in the development and progression of NSCLC using clinical samples and NSCLC cell lines. The results show that upregulated KLHL17 in NSCLC promotes the proliferation and migration of tumor by activating Ras/MAPK signaling pathway, and suggest that KLHL17 may be a novel therapeutic target for the treatment of NSCLC.
LABORATORY INVESTIGATION
(2022)
Article
Chemistry, Medicinal
Fanye Meng, Chenxi Xu, Kwang-Su Park, H. Umit Kaniskan, Gang Greg Wang, Jian Jin
Summary: In this study, a first-in-class NSD2 proteolysis targeting chimera (PROTAC) degrader was discovered, which effectively degraded NSD2 and CRBN. This compound was more effective in suppressing cancer cell growth compared to existing inhibitors and showed bioavailability in mice.
JOURNAL OF MEDICINAL CHEMISTRY
(2022)
Review
Cell Biology
Fumiyo Ikeda
Summary: Ubiquitin modifies diverse substrates through various conjugation types, regulating a wide range of biological functions. While the C-terminus of ubiquitin traditionally forms isopeptide or peptide bonds with protein substrates, recent studies have revealed that it can also form atypical oxyester bonds, targeting both proteinaceous and nonproteinaceous substrates such as sugars and lipids. The understanding of how nonprotein ubiquitination affects substrate and cellular functions is still incomplete. This review discusses recent discoveries in ubiquitination and its potential impacts on biology.
AMERICAN JOURNAL OF PHYSIOLOGY-CELL PHYSIOLOGY
(2023)
Article
Chemistry, Medicinal
Serah W. Kimani, Julie Owen, Stuart R. Green, Fengling Li, Yanjun Li, Aiping Dong, Peter J. Brown, Suzanne Ackloo, David Kuter, Cindy Yang, Miranda MacAskill, Stephen Scott MacKinnon, Cheryl H. Arrowsmith, Matthieu Schapira, Vijay Shahani, Levon Halabelian
Summary: DCAF1 serves as a subunit for RING-type CRL4(DCAF1) and HECT family EDVPDCAF1 E3 ubiquitin ligases in substrate recruitment. The WDR domain of DCAF1 acts as a binding platform for substrate proteins and is targeted by HIV and SIV lentiviral adaptors. This study used a proteome-scale drug-target interaction prediction model to identify ligands for the DCAF1 WDR domain through biophysical screening and X-ray crystallography, confirming the selective binding of a predicted ligand. The findings demonstrate the successful application of artificial intelligence-enabled virtual screening methods in the absence of previously known ligands.
JOURNAL OF CHEMICAL INFORMATION AND MODELING
(2023)
Review
Immunology
Haoran Cui, Yaxian Zhang, Leiliang Zhang
Summary: Poxviruses have evolved various mechanisms to evade innate immunity, some of which involve poxvirus-encoded E3 ubiquitin ligases and adaptor proteins. These proteins can be categorized into five groups based on their functional domains and ubiquitin transfer mechanisms. Most known substrates of poxvirus E3 ubiquitin ligases are components of the innate immune system. Current research progress provides mechanistic insights into the interaction between these viruses and their hosts.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Virology
Nora Freudenberger, Tina Meyer, Peter Groitl, Thomas Dobner, Sabrina Schreiner
JOURNAL OF VIROLOGY
(2018)
Article
Virology
Raviteja Inturi, Kwangchol Mun, Katrin Singethan, Sabrina Schreiner, Tanel Punga
JOURNAL OF VIROLOGY
(2018)
Article
Virology
Gabriele Stakaityte, Nnenna Nwogu, Samuel J. Dobson, Laura M. Knight, Christopher W. Wasson, Francisco J. Salguero, David J. Blackbourn, G. Eric Blair, Jamel Mankouri, Andrew Macdonald, Adrian Whitehouse
JOURNAL OF VIROLOGY
(2018)
Review
Virology
Sabrina Schreiner, Michael Nassal
Article
Biochemistry & Molecular Biology
Gabriele Stakaityte, Nnenna Nwogu, Jonathan D. Lippiat, G. Eric Blair, Krzysztof Poterlowicz, James R. Boyne, Andrew Macdonald, Jamel Mankouri, Adrian Whitehouse
JOURNAL OF BIOLOGICAL CHEMISTRY
(2018)
Article
Virology
Sarah Muencheberg, Ron T. Hay, Wing H. Ip, Tina Meyer, Christina Weiss, Jara Brenke, Sawinee Masser, Kamyar Hadian, Thomas Dobner, Sabrina Schreiner
JOURNAL OF VIROLOGY
(2018)
Article
Virology
Anna Reichel, Anne-Charlotte Stilp, Myriam Scherer, Nina Reuter, Soeren Lukassen, Bahram Kasmapour, Sabrina Schreiner, Luka Cicin-Sain, Andreas Winterpacht, Thomas Stamminger
JOURNAL OF VIROLOGY
(2018)
Article
Virology
James S. Findlay, Graham P. Cook, G. Eric Blair
Article
Microbiology
Nnenna Nwogu, James R. Boyne, Samuel J. Dobson, Krzysztof Poterlowicz, G. Eric Blair, Andrew Macdonald, Jamel Mankouri, Adrian Whitehouse
Article
Chemistry, Multidisciplinary
Samuel Hofmann, Julia Mai, Sawinee Masser, Peter Groitl, Alexander Herrmann, Thomas Sternsdorf, Ruth Brack-Werner, Sabrina Schreiner
Article
Microbiology
Ethan L. Morgan, Molly R. Patterson, Emma L. Ryder, Siu Yi Lee, Christopher W. Wasson, Katherine L. Harper, Yigen Li, Stephen Griffin, G. Eric Blair, Adrian Whitehouse, Andrew Macdonald
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
Microbiology
Laura White, Bilgi Erbay, G. Eric Blair
Summary: Cajal bodies can be reorganized into microfoci during adenovirus infection. The protein p80-coilin forms a complex with L4-22K protein, facilitating the nuclear export of Ad mRNA.
Article
Biology
Peter A. C. Wing, Tamara Davenne, Jochen Wettengel, Alvina G. Lai, Xiaodong Zhuang, Anindita Chakraborty, Valentina D'Arienzo, Catharina Kramer, Chunkyu Ko, James M. Harris, Sabrina Schreiner, Martin Higgs, Stephanie Roessler, Joanna L. Parish, Ulrike Protzer, Peter Balfe, Jan Rehwinkel, Jane A. McKeating
LIFE SCIENCE ALLIANCE
(2019)