Article
Biochemistry & Molecular Biology
Fumi Kozu, Kanae Shirahama-Noda, Yasuhiro Araki, Shintaro Kira, Hitoshi Niwa, Takeshi Noda
Summary: In this study, the effects of the inhalation anesthetic isoflurane on membrane proteins were examined using yeast cells. The results indicate that isoflurane affects the amino acid transporter Bap2 through an Art2-Rsp5 dependent ubiquitination system.
Article
Cardiac & Cardiovascular Systems
Bethan L. Clifford, Kelsey E. Jarrett, Joan Cheng, Angela Cheng, Marcus Seldin, Pauline Morand, Richard Lee, Mary Chen, Angel Baldan, Thomas Q. de Aguiar Vallim, Elizabeth J. Tarling
Summary: This study reveals a novel role of RNF130 in regulating LDL-C levels by modulating the availability of LDLR.
CIRCULATION RESEARCH
(2023)
Article
Biology
Natalya Pashkova, Lokesh Gakhar, Liping Yu, Nicholas J. Schnicker, Annabel Y. Minard, Stanley Winistorfer, Ivan E. Johnson, Robert C. Piper
Summary: The study reveals that ubiquitinated membrane proteins can interact with multiple components of the internalization apparatus, including CALM, HIP1R, and Sla2, by binding to their N-terminal ANTH domain. These findings define new components of the internalization machinery that work collectively with Epsin and Eps15 to specify recognition of Ub as an internalization signal.
Review
Biochemistry & Molecular Biology
Liuqin Zhang, Yifan Guo, Yujie Zhang, Yuxin Li, Yan Pei, Mi Zhang
Summary: The action of auxin largely depends on the establishment of auxin concentration gradient within plant organs, where PIN-mediated directional auxin movement plays an important role. Recent studies have highlighted the importance of PIN degradation in reestablishing auxin gradient. This review summarizes the current understanding on controlling PIN degradation and discusses the possible mechanisms.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Review
Cell Biology
Min Wu, Xudong Wu
Summary: The essay explores how the concept of kinetic proofreading could be applied to cargo sorting in clathrin-mediated endocytosis, highlighting the importance of regulating equilibrium binding affinity or proofreading mechanisms to achieve specificity and sensitivity in biochemical reactions.
CURRENT OPINION IN CELL BIOLOGY
(2021)
Review
Cell Biology
Sara E. Hanley, Katrina F. Cooper
Summary: Protein homeostasis is maintained by three major pathways including the ubiquitin-proteasome system, autophagy-lysosomal pathway, and endo-lysosomal pathway. Sorting nexins, a family of membrane-associated proteins, play important roles in protein trafficking and maintaining protein quality control mechanisms by connecting with ubiquitin. Defects in sorting nexins are associated with a range of human diseases, highlighting their critical roles in cellular function.
Article
Multidisciplinary Sciences
Ji-Ung Jung, Melanie H. Cobb
Summary: The protein kinase WNK1 influences the trafficking and actin polymerization of membrane proteins. This study discovered a connection between WNK1 and TRIM27, which regulates endosomal actin polymerization. Depletion of WNK1 disrupted WASH ubiquitination and endosomal actin polymerization, affecting endosomal trafficking. Depletion of WNK1 or TRIM27 increased the degradation of EGFR in cancer cells.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2023)
Article
Cell Biology
Guanlin Li, Yongqing Wang, Guangming Cao, Yeling Ma, Yu-Xia Li, Yangyu Zhao, Xuan Shao, Yan-Ling Wang
Summary: This study reveals that prolonged hypoxic stress induces increased endocytosis and repression of ubiquitin-mediated Met degradation, leading to impaired regulation of trophoblast invasion by HGF/Met signaling. These findings provide novel evidence for elucidating the pathogenesis of preeclampsia, especially of the early-onset subtype.
JOURNAL OF BIOMEDICAL SCIENCE
(2022)
Article
Biochemistry & Molecular Biology
Fumiyo Ikeda
Summary: The ubiquitin-proteasomal system and the autophagy-lysosome system are two major degradation systems in mammalian cells. Ubiquitin not only regulates proteasomal degradation of substrates but also regulates the autophagy pathway. Ubiquitin plays a key role in autophagy regulation by recruiting cargos to phagophore in a ubiquitin-dependent manner.
Article
Multidisciplinary Sciences
Seung-Ryoung Jung, Yifei Jiang, Jong Bae Seo, Daniel T. Chiu, Bertil Hille, Duk-Su Koh
Summary: ?-Arrestins play a role in promoting the synthesis of PI(4,5)P2 and up-regulating GPCR endocytosis, by coordinating potentiation of PIP5K activity at clathrin-coated pits (CCPs) to induce local PI(4,5)P2 generation that promotes recruitment of PI(4,5)P2-dependent endocytic machinery.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Article
Biochemistry & Molecular Biology
Abramo J. Manfredonia, Daniel A. Kraut
Summary: The ubiquitin-proteasome system is responsible for protein degradation in eukaryotic cells. The study showed that degradation of ubiquitin-independent degrons (UbIDs) is slower and relies on loosely folded substrates. Furthermore, UbID degradation is ATP-independent.
Article
Multidisciplinary Sciences
Rosalind L. Ang, Mark Chan, Diana Legarda, John P. Sundberg, Shao-Cong Sun, Virginia L. Gillespie, Nicholas Chun, Peter S. Heeger, Huabao Xiong, Sergio A. Lira, Adrian T. Ting
Summary: The study found that the phenotype of Sharpin(cpdm/cpdm) mice is dependent on CYLD, which suppresses TNF- and RIPK1-dependent cell death. Regulation of CYLD can ameliorate inflammatory symptoms such as dermatitis in mice.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Review
Biochemistry & Molecular Biology
Samantha De La-Rocque, Edoardo Moretto, Ioana Butnaru, Giampietro Schiavo
Summary: The presence and distribution of tau in the brain of AD patients are closely related to cognitive decline, more so than amyloid plaque deposition. Tau pathology can spread within the central nervous system via a prion-like mechanism, showing a stereotypical pattern and involving trans-synaptic inter-neuronal transfer.
JOURNAL OF NEUROCHEMISTRY
(2021)
Review
Biochemistry & Molecular Biology
Kevin G. Mark, Michael Rape
Summary: Research has shown that ubiquitylation plays a crucial role in transcription, ensuring the correct expression of genes during development. Disruption of these regulatory circuits can lead to a wide array of human diseases.
Article
Multidisciplinary Sciences
Hongbin Li, Vishaal Rajani, Lu Han, Danielle Chung, James E. Cooke, Ameet S. Sengar, Michael W. Salter
Summary: NMDA receptors (NMDARs) are a principal subtype of excitatory neurotransmitter receptor, composed of two GluN1 and two GluN2 subunits. Alternative splicing of GluN1 can affect the signaling of glycine, which is crucial for the nonionotropic signaling by NMDARs.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Article
Biochemistry & Molecular Biology
Andrea Gubas, Ivan Dikic
Summary: Autophagy is a highly conserved cellular process for degrading abnormal cellular components and foreign pathogens, which can be selective or nonselective. Autophagy receptors play a crucial role in linking and degrading cell components during autophagy, undergoing structural modifications to fulfill their function.
Article
Biochemistry & Molecular Biology
Benedikt Linder, Caterina Klein, Marina E. Hoffmann, Florian Bonn, Ivan Dikic, Donat Koegel
Summary: By regulating hallmarks of cancer, BAG3 plays oncogenic roles in various malignant diseases, and its knockdown enhances ciliogenesis and reduces cell migration.
JOURNAL OF CELLULAR BIOCHEMISTRY
(2022)
Article
Biochemistry & Molecular Biology
Cristian Prieto-Garcia, Oliver Hartmann, Michaela Reissland, Thomas Fischer, Carina R. Maier, Mathias Rosenfeldt, Christina Schuelein-Voelk, Kevin Klann, Reinhard Kalb, Ivan Dikic, Christian Munch, Markus E. Diefenbacher
Summary: Squamous cell carcinomas (SCC) exhibit high mutational burden and platinum-based chemotherapy resistance, with increased Np63 expression associated with resistance; USP28 is recruited to sites of DNA damage and plays a regulatory role in DNA damage repair in SCC; Targeting the USP28- increment Np63 axis can overcome chemotherapy resistance in SCC.
CELL DEATH AND DIFFERENTIATION
(2022)
Review
Biochemistry & Molecular Biology
Andrea Gubas, Ivan Dikic
Summary: The endoplasmic reticulum (ER) is involved in many essential cellular processes, including ER-phagy. ER-phagy is a process that selectively degrades ER fragments to maintain ER size and morphology, and it relies on specialized ER-shaping proteins. This review provides insights into the membrane remodeling mechanisms of ER-phagy and emphasizes its significance in human physiology and pathology.
Article
Microbiology
Varnesh Tiku, Chun Kew, Eric M. Kofoed, Yutian Peng, Ivan Dikic, Man-Wah Tan
Summary: This study reveals that A. baumannii secretes an inflammatory bioactive lipid that activates multiple pro-inflammatory signaling pathways and induces cell death. This finding contributes to a better understanding of the immune mechanisms involved in A. baumannii infection.
FRONTIERS IN MICROBIOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Chun-Che Tseng, Robert C. Piper, David J. Katzmann
Summary: The Endosomal Sorting Complexes Required for Transport (ESCRTs) play a crucial role in membrane remodeling during cellular processes. Recent research has uncovered the ability of Bro1, an ESCRT-associated Ub-binding protein, to coordinate ESCRT-III and Vps4-dependent intralumenal vesicle (ILV) biogenesis, as well as its involvement in upstream events such as cargo recognition.
Review
Cell Biology
Ivan Dikic, Brenda A. Schulman
Summary: Recent studies have advanced our understanding of ubiquitylation, revealing unconventional ubiquitylation mechanisms used by pathogens to promote infection. Structural studies have shown that ubiquitin functions involve complex multivalent interactions that regulate transcription or protein degradation. Furthermore, these interactions can induce conformational changes and regulate protein degradation or transcription. These newly discovered mechanisms provide potential opportunities for innovative therapeutic interventions for diseases such as cancer and infectious diseases.
NATURE REVIEWS MOLECULAR CELL BIOLOGY
(2023)
Article
Chemistry, Multidisciplinary
David A. Perez A. Berrocal, Thimmalapura M. Vishwanatha, Daniel Horn-Ghetko, J. Josephine Botsch, Laura A. Hehl, Sebastian Kostrhon, Mohit Misra, Ivan Dikic, Paul P. Geurink, Hans van Dam, Brenda A. Schulman, Monique P. C. Mulder
Summary: Protein post-translational modification with ubiquitin (Ub) is a versatile signal regulating cell biology, and diseases associated with impaired Ub modification present opportunities for novel targeted treatments. The final components of the ubiquitination cascade, E3 ligases, have potential as small molecule targets. UbSRhodol, an autoimmolative Ub-based probe, enables detection of changes in E3 transthiolation activity, making it suitable for high-throughput screening and identification of small molecules modulating E3 activity.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2023)
Editorial Material
Biochemistry & Molecular Biology
Angus I. Lamond, Ivan Dikic, Andre Nussenzweig, Christoph W. Mueller, Janet M. Thornton, Michael B. Yaffe
Article
Cell Biology
Anshu Bhattacharya, Rukmini Mukherjee, Santosh Kumar Kuncha, Melinda Elaine Brunstein, Rajeshwari Rathore, Stephan Junek, Christian Muench, Ivan Dikic
Summary: Acute lysosomal membrane damage reduces functional lysosomes, but they have a recovery potential independent of lysosomal biogenesis and remain unaffected in cells depleted in TFEB and TFE3. A lysosomal membrane regeneration pathway was discovered that depends on ATG8, LIMP2, TBC1D15, dynamin-2, kinesin-5B, and clathrin. LIMP2 acts as a lysophagy receptor, binding ATG8, which recruits TBC1D15 to damaged lysosomal membranes. TBC1D15 interacts with ATG8 proteins and stabilizes the autophagic lysosomal reformation machinery, promoting lysosomal tubule formation and dynamin-2-dependent scission.
NATURE CELL BIOLOGY
(2023)
Article
Clinical Neurology
Christopher P. Ptak, Tabitha A. Peterson, Jesse B. Hopkins, Christopher A. Ahern, Michael E. Shy, Robert C. Piper
Summary: Mutations in MPZ can cause various neurological disorders, and the study focuses on understanding how MPZ functions and forms oligomeric assemblies.
Review
Immunology
Joao Mello-Vieira, Tobias Bopp, Ivan Dikic
Summary: Cell-autonomous immunity is the first line of defense for cells to recognize and eliminate invasive pathogens. Ubiquitination plays a crucial role in orchestrating immune signaling networks and stimulating the appropriate immune response. This review focuses on how ubiquitin connects pathogen sensing pathways to cellular responses and discusses therapeutic options for enhancing cell-autonomous immune responses.
CURRENT OPINION IN IMMUNOLOGY
(2023)
Article
Urology & Nephrology
Hua Sun, Jillian Weidner, Chantal Allamargot, Robert C. Piper, Jason Misurac, Carla Nester
Summary: Dynein-mediated trafficking of nephrin to lysosomes is stimulated by hyperglycemia, leading to its degradation. This finding provides new therapeutic targets for diabetic nephropathy.
Article
Cell Biology
Alexis Gonzalez, Ivan Dikic
Meeting Abstract
Oncology
Alicia Haydo, Johanna Ertl, Jennifer Schmidt, Marina E. Hoffmann, Stephanie Hehlgans, Alisha Crider, Rajeshwari Rathore, Christel Herold-Mende, Ivan Dikic, Mingji Dai, Alexander Adibekian, Franz Roedel, Donat Koegel, Benedikt Linder
STRAHLENTHERAPIE UND ONKOLOGIE
(2023)