Article
Biochemistry & Molecular Biology
Nicholas W. Ashton, Gabrielle J. Valles, Nancy Jaiswal, Irina Bezsonova, Roger Woodgate
Summary: USP7 is a critical deubiquitinating enzyme with important roles in multiple signaling pathways. The study reveals that DNA polymerase iota is a novel substrate of USP7, which requires binding to both TRAF and UBL1-2 domains for efficient deubiquitination. This discovery establishes a new bipartite mode of substrate binding for USP7.
JOURNAL OF MOLECULAR BIOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Chia-Cheng Kan, Azucena Mendoza-Herrera, Julien Levy, J. Joe Hull, Jeffery A. Fabrick, Cecilia Tamborindeguy
Summary: This study identified HPE1 as a suppressor of plant immunity and showed its interaction with tomato RAD23 proteins, suggesting a role in virulence in Lso pathogenesis by perturbing the ubiquitin-proteasome system. The study also observed earlier colonization and symptom development in HPE1 overexpressing plants infected with Lso haplotype B.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Biology
Alessandro Stirpe, Nora Guidotti, Sarah J. Northall, Sinan Kilic, Alexandre Hainard, Oscar Vadas, Beat Fierz, Thomas Schalch
Summary: Research has shown that ubiquitination of lysine 14 on histone H3 (H3K14ub) plays a key role in H3K9 methylation in the fission yeast. The SET domain of Clr4 harbors a conserved sensor for H3K14ub, which mediates licensing of heterochromatin formation.
Article
Biochemistry & Molecular Biology
Adam J. Middleton, Fareeda M. Barzak, Thornton J. Fokkens, Khanh Nguyen, Catherine L. Day
Summary: Inflammation is crucial for immune function, wound healing, and infection resolution. RNF125, an E3 ubiquitin ligase, plays a critical role in attenuating RIG-I signaling, although the mechanisms are not well understood. This study reveals that RNF125's E3 ligase activity relies on its zinc finger domain (ZF1) and RING domain, and that ZF1 recruits the E2 protein while residues N-terminal to the RING domain activate the E2-Ub conjugate. These findings shed light on the termination of RIG-I dependent inflammatory responses and the contribution of RNF125 to disease. Moreover, this study uncovers a new role for ZF domains in E3 ligases.
Article
Plant Sciences
Konstantin Kerner, Soshichiro Nagano, Annika Lubbe, Ute Hoecker
Summary: The study found that the WD repeat of SPA1 is essential for the activity of COP1/SPA, while the WD repeat of COP1 is partially dispensable. A complex with four SPA1-WDs is more active than a complex with only two SPA1-WDs.
PLANT CELL AND ENVIRONMENT
(2021)
Article
Multidisciplinary Sciences
Yu-Han Lin, Meng-Yun Xu, Chuan-Chih Hsu, Florensia Ariani Damei, Hui-Chun Lee, Wei-Lun Tsai, Cuong V. Hoang, Yin-Ru Chiang, Lay-Sun Ma
Summary: This study reveals the role of fungal PR-1-like proteins in countering plant defense, and how Ustilago maydis utilizes plant proteases to promote fungal virulence.
NATURE COMMUNICATIONS
(2023)
Article
Plant Sciences
Sujit Jung Karki, Aisling Reilly, Binbin Zhou, Maurizio Mascarello, James Burke, Fiona Doohan, Dimitar Douchkov, Patrick Schweizer, Angela Feechan
Summary: Septoria tritici blotch (STB) caused by Zymoseptoria tritici is a major threat to wheat production worldwide. The study identified a conserved cysteine-rich secreted effector, ZtSSP2, from Z. tritici, which interacts with wheat E3 ubiquitin ligase (TaE3UBQ) and may play a role in wheat immunity against the fungus. Further research is needed to understand the mechanisms of this interaction and potential implications for disease resistance in wheat.
JOURNAL OF EXPERIMENTAL BOTANY
(2021)
Article
Multidisciplinary Sciences
Sei Samukawa, Ryusuke Yoshimi, Yohei Kirino, Hideaki Nakajima
Summary: The study revealed that beta 2MG serves as a ligand for Pyrin, inducing Pyrin inflammasome formation, and FMF-associated Pyrin mutations weaken the negative feedback loop of caspase-1 p20 subunit.
SCIENTIFIC REPORTS
(2021)
Article
Endocrinology & Metabolism
Thanh N. Dang, Jessica L. Taylor, Gail Kilroy, Yongmei Yu, David H. Burk, Z. Elizabeth Floyd
Summary: SIAH2 is expressed in adipocyte precursor cells and interacts with EBF1 and ZFP521 to enhance the degradation of ZFP521 while increasing EBF1 levels, revealing its role in regulating adipogenesis.
Article
Biology
Aiqin Sun, Jun Zhu, Song Xia, Yanling Li, Tiantian Wu, Genbao Shao, Wannian Yang, Qiong Lin
Summary: The study revealed that NEDD4 interacts with MEKK5 through a conserved WW3 domain, but MEKK5 is not a ubiquitination substrate of NEDD4 and instead negatively regulates NEDD4-mediated ubiquitination. Overexpression of MEKK5 significantly reduces NEDD4-promoted lung cancer cell migration.
Article
Biology
Min-Duk Seo, Seung-Hyeon Seok, Ji-Hun Kim, Ji Woong Choi, Sung Jean Park, Bong-Jin Lee
Summary: The study elucidated the interactions and binding mode between LMP2A and Nedd4 family E3 ubiquitin-protein ligases, showing that the PY motifs of LMP2A weakly interact with the XP groove of the WW2 domain. The unique changes in the hairpin loop region of the WW2 domain suggest its role in stabilizing the complex formed between the PY and WW domains.
Article
Plant Sciences
Ross D. Etherington, Mark Bailey, Jean-Baptiste Boyer, Laura Armbruster, Xulyu Cao, Juliet C. Coates, Thierry Meinnel, Markus Wirtz, Carmela Giglione, Daniel J. Gibbs
Summary: This study reveals that Arabidopsis DOA10A-like E3 ligases regulate the turnover of SQUALENE EPOXIDASE 1 independently of the Ac/N-degron pathway. It also shows that DOA10 E3 ligases in Arabidopsis are not major players in the degradation of N-acetylated proteins.
Article
Oncology
Anni Laine, Srikar G. Nagelli, Caroline Farrington, Umar Butt, Anna N. Cvrljevic, Julia P. Vainonen, Femke M. Feringa, Tove J. Gronroos, Prson Gautam, Sofia Khan, Harri Sihto, Xi Qiao, Karolina Pavic, Denise C. Connolly, Pauliina Kronqvist, Laura L. Elo, Jochen Maurer, Krister Wennerberg, Rene H. Medema, Heikki Joensuu, Emilia Peuhu, Karin de Visser, Goutham Narla, Jukka Westermarck
Summary: CIP2A plays a crucial role in basal-like breast cancer by influencing DNA damage-induced mitotic checkpoint and cell proliferation, driving disease initiation and progression.
Article
Biochemistry & Molecular Biology
Andrew J. Boughton, Daoning Zhang, Rajesh K. Singh, David Fushman
Summary: Proteasome-mediated substrate degradation relies on the coordinated actions of ubiquitin, UBL-containing shuttle proteins, and the proteasome. Research indicates that the proteasomal subunit Rpn1 associates with UBL-containing proteins and polyUb chains.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2021)
Article
Cell Biology
Jing Wang, Dawadschargal Dubiel, Yanmeng Wu, Yabin Cheng, Dieter A. Wolf, Wolfgang Dubiel
Summary: CSN7A and CSN7B have overlapping functions in deneddylation, but CSN7B plays a unique role in DNA damage sensing and affects DNA repair pathway choice; knockout of CSN7B leads to resistance to DNA damage and a switch in DNA repair pathway.
Article
Biochemistry & Molecular Biology
Shubo Zhao, Anja Kieser, Hao-Yi Li, Hannah K. Reinking, Pedro Weickert, Simon Euteneuer, Denitsa Yaneva, Aleida C. Acampora, Maximilian J. Goetz, Regina Feederle, Julian Stingele
Summary: A ubiquitin switch negatively regulates the metalloprotease SPRTN by inducing monoubiquitylation, leading to enzyme inactivation through autocatalytic cleavage and proteasomal degradation. The deubiquitylating enzyme USP7 antagonizes this negative control of SPRTN in the presence of covalent DNA-protein crosslinks (DPCs).
NUCLEIC ACIDS RESEARCH
(2021)
Review
Biochemistry & Molecular Biology
Pedro Weickert, Julian Stingele
Summary: This review provides an overview of the sources and principles of cellular DPC formation, as well as the cellular mechanisms resolving these threats to genomic integrity. Repair of DPCs requires the action of canonical DNA repair pathways and specialized proteolytic enzymes. Loss of DPC repair capacity has dramatic consequences.
ANNUAL REVIEW OF BIOCHEMISTRY
(2022)
Editorial Material
Biochemistry & Molecular Biology
Maximilian J. Gotz, Julian Stingele
Summary: Krastev et al. have identified a cellular mechanism that can counteract cytotoxic trapping of PARP1 induced by clinical PARP inhibitors. They found that SUMO-targeted ubiquitylation of trapped PARP1 triggers its extraction from chromatin by the p97 ATPase.
Article
Biochemistry & Molecular Biology
Carolin P. M. Scheitl, Mateusz Mieczkowski, Hermann Schindelin, Claudia Hoebartner
Summary: RNA-catalyzed RNA methylation has been found to be part of the catalytic repertoire of ribozymes. The crystal structure of methyltransferase ribozyme MTR1 has been determined, revealing a guanine-binding site similar to natural guanine riboswitches. The structure also suggests the involvement of a protonated cytidine in the methyl transfer reaction. The synergistic effect of 2'-O-methylated ribose residues in the active site accelerates methyl group transfer. These findings suggest that modified nucleotides may have played a role in early RNA catalysis and that metabolite-binding riboswitches resemble inactivated ribozymes.
NATURE CHEMICAL BIOLOGY
(2022)
Article
Microbiology
Philip Eisenberg, Leon Albert, Jonathan Teuffel, Eric Zitzow, Claudia Michaelis, Jane Jarick, Clemens Sehlke, Lisa Grosse, Nicole Bader, Ariane Nunes-Alves, Bernd Kreikemeyer, Hermann Schindelin, Rebecca C. Wade, Tomas Fiedler
Summary: The study reveals the importance of the non-phosphorylating glyceraldehyde-3-phosphate dehydrogenase GapN in Streptococcus pyogenes and its potential as a target for antimicrobial substances that selectively kill S. pyogenes and other streptococci.
FRONTIERS IN MICROBIOLOGY
(2022)
Article
Multidisciplinary Sciences
Ngoc Truongvan, Shurong Li, Mohit Misra, Monika Kuhn, Hermann Schindelin
Summary: UBA6 is an E1 enzyme that can activate both ubiquitin and FAT10. Here, the authors employ X-ray crystallography and biochemical techniques to explain this dual specificity, and identify UBA6 variants that are selectively impaired in the activation of either ubiquitin or FAT10.
NATURE COMMUNICATIONS
(2022)
Article
Neurosciences
Nasir Imam, Susobhan Choudhury, Katrin G. Heinze, Hermann Schindelin
Summary: Interneuronal synaptic transmission relies on the proper organization of neurotransmitter release and reception. Inhibitory GABAergic postsynapses involve the recruitment of collybistin, a neuronal adaptor protein, which interacts with various proteins including cell adhesion proteins of the neuroligin family and GABA(A) receptors. Furthermore, TC10 can induce the activation of collybistin, leading to a switch from its closed/inactive state to an open/active state.
FRONTIERS IN SYNAPTIC NEUROSCIENCE
(2022)
Article
Biochemistry & Molecular Biology
Pia Maria van gen Hassend, Aparna Pottikkadavath, Carolyn Delto, Monika Kuhn, Michelle Endres, Lars Schoenemann, Hermann Schindelin
Summary: The CTLH complex is a multisubunit RING E3 ligase with flexible subunit composition and poorly defined substrate specificity. By using various biophysical and biochemical techniques, we characterized the assembly pathways of the CTLH complex, focusing on key subunits Wdr26, muskelin, RanBP9, Twa1, and Armc8 beta. Our study revealed that muskelin tetramerization and Wdr26 dimer assembly define mutually exclusive oligomerization modules that compete for binding to RanBP9. Additionally, we found that RanBP9 organizes subunit assembly and prevents higher order oligomerization of Wdr26 and the Armc8 beta-Twa1 heterodimer. These findings advance our understanding of the CTLH complex architectures.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2023)
Article
Biochemistry & Molecular Biology
Denitsa Yaneva, Justin L. Sparks, Maximilian Donsbach, Shubo Zhao, Pedro Weickert, Rachel Bezalel-Buch, Julian Stingele, Johannes C. Walter
Summary: Endogenous and exogenous agents generate DNA-protein crosslinks (DPCs), whose replication-dependent degradation by the SPRTN protease suppresses aging and liver cancer. In this study, it is found that the helicase FANCJ plays a role in DPC repair by binding to ssDNA downstream of the DPC and using its ATPase activity to unfold the protein adduct, enabling cleavage of the adduct and facilitating translesion DNA synthesis past DPCs that cannot be degraded. These findings highlight the importance of helicase-mediated protein unfolding in DPC repair.
Article
Multidisciplinary Sciences
Elisabeth Jeanclos, Jan Schloetzer, Kerstin Hadamek, Natalia Yuan-Chen, Mohammad Alwahsh, Robert Hollmann, Stefanie Fratz, Dilan Yesilyurt-Gerhards, Tina Frankenbach, Daria Engelmann, Angelika Keller, Alexandra Kaestner, Werner Schmitz, Martin Neuenschwander, Roland Hergenroeder, Christoph Sotriffer, Jens Peter von Kries, Hermann Schindelin, Antje Gohla
Summary: This study demonstrates the druggability of phosphoglycolate phosphatase and validates an alternative approach to control glycolysis. The compound CP1 inhibits the phosphatase and replicates the effects of cellular PGP-deficiency, providing key insights into effective and precise targeting of PGP.
NATURE COMMUNICATIONS
(2022)
Article
Multidisciplinary Sciences
Pedro Weickert, Hao-Yi Li, Maximilian J. Goetz, Sophie Duerauer, Denitsa Yaneva, Shubo Zhao, Jacqueline Cordes, Aleida C. Acampora, Ignasi Forne, Axel Imhof, Julian Stingele
Summary: DNA-protein crosslinks (DPCs) are common DNA lesions induced by reactive metabolites and chemotherapeutic agents. A novel technique called PxP is developed to identify and track different types of DPCs in mammalian cells. The study reveals an unexpected role for the SPRTN protease in replication-independent repair of DPCs and demonstrates the mechanisms involved.
NATURE COMMUNICATIONS
(2023)
Article
Chemistry, Multidisciplinary
Sebastian Bothe, Petra Haenzelmann, Stephan Boehler, Josef Kehrein, Markus Zehe, Christoph Wiedemann, Ute A. Hellmich, Ruth Brenk, Hermann Schindelin, Christoph Sotriffer
Summary: Biosensor techniques are increasingly important in fragment-based drug discovery, and the AAA+ ATPase p97 is a key protein that could be targeted for cancer chemotherapy. Current p97 inhibitors have broad effects, but we have identified a protein-protein interaction inhibitor that can selectively target specific p97 functions.
COMMUNICATIONS CHEMISTRY
(2022)
Article
Biochemistry & Molecular Biology
Maximilian Donsbach, Sophie Duerauer, Florian Gruenert, Kha T. Nguyen, Richa Nigam, Denitsa Yaneva, Pedro Weickert, Rachel Bezalel-Buch, Daniel R. Semlow, Julian Stingele
Summary: The protein HMCES crosslinks to AP sites in ssDNA to prevent DNA breaks. We discovered a non-proteolytic release mechanism for HMCES-DPCs, regulated by DNA context. HMCES-DPCs are stable in ssDNA but released in dsDNA, allowing downstream repair.
Article
Biophysics
Nasir Imam, Susobhan Choudhury, Katherina Hemmen, Katrin G. Heinze, Hermann Schindelin
Summary: Efficient neuronal signaling relies on proper assembly of synaptic neurotransmitter machinery. This study elucidates the molecular basis and regulation of the interaction between gephyrin and colbybistin, which play key roles in GABAergic synapses.
BIOPHYSICAL REPORTS
(2022)
Article
Biochemical Research Methods
Niels Bauer, Benedikt Oswald, Maximilian Eiche, Lisa Schiller, Emma Langguth, Christian Schantz, Andrea Osterlehner, Amy Shen, Shahram Misaghi, Julian Stingele, Simon Auslaender
Summary: The depletion of the Myc gene using CRISPR/Cas9 technology significantly increases the production yield of complex antibody formats in Chinese Hamster Ovary (CHO) cells without impairing product quality. This finding sheds light on the relationship between cell growth and production and offers a targeted cell engineering approach to enhance the manufacturing yield of high-value complex biotherapeutics.