Article
Biochemistry & Molecular Biology
Jyoti Gupta, Erumbi S. Rangarajan, Regina B. Troyanovsky, Indrajyoti Indra, Sergey M. Troyanovsky, Tina Izard
Summary: This article reports on the novel properties of plakophilin-3, a widely expressed protein in epithelial cells and a critical component of desmosomes. The study found that the armadillo repeat motif domain of plakophilin-3 is a monomer or homodimer in solution, and it directly interacts with F-actin. It was also discovered that plakophilin-3 can be recruited to the plasma membrane through phosphatidylinositol-4,5-bisphosphate-mediated interactions. These findings contribute to understanding the role of plakophilin-3 in cell-cell adhesion.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Cardiac & Cardiovascular Systems
Marina Cerrone, Grecia M. Marron-Linares, Chantal J. M. van Opbergen, Sarah Costa, Mimount Bourfiss, Marta Perez-Hernandez, Florencia Schlamp, Fabian Sanchis-Gomar, Kabir Malkani, Kamelia Drenkova, Mingliang Zhang, Xianming Lin, Adriana Heguy, Birgitta K. Velthuis, Niek H. J. Prakken, Andre LaGerche, Hugh Calkins, Cynthia A. James, Anneline S. J. M. Te Riele, Mario Delmar
Summary: Exercise increases the risk of arrhythmia and progression of cardiomyopathy in ARVC patients, and transcriptomic changes caused by endurance training in mice deficient in PKP2 reveals similarities to sedentary and exercised PKP2cKO mice. PKP2 loss leads to cardiac contractile deficit, decreased muscle mass, and increased functional/transcriptomic signatures of apoptosis. Additionally, cardiac dimensions in human athletes carrying PKP2 mutations are reduced compared to matched controls.
EUROPEAN HEART JOURNAL
(2022)
Article
Anatomy & Morphology
Sunil Yeruva, Jens Waschke
Summary: Comparative analysis of cell contacts in cardiomyocytes and epithelial cells can help to better understand the pathogenesis of cardiovascular and dermatological diseases.
JOURNAL OF ANATOMY
(2023)
Article
Cell Biology
Judith B. Fulle, Henri Huppert, David Liebl, Jaron Liu, Rogerio Alves de Almeida, Bian Yanes, Graham D. Wright, E. Birgitte Lane, David R. Garrod, Christoph Ballestrem
Summary: This study investigated the structure and turnover process of desmosomes, revealing that desmosomes consist of stable protein moieties and highly mobile protein moieties. The findings suggest the presence of both stable and mobile modules during the dynamic changes in desmosomes.
JOURNAL OF CELL SCIENCE
(2021)
Article
Cell Biology
Lisa Mueller, Rene Keil, Mechthild Hatzfeld
Summary: PKP3, an overexpressed component of desmosomes in cancer, controls the signaling axis from ERK to RB protein and E2F1 transcription factor, promoting cell cycle transition and proliferation.
Article
Biochemistry & Molecular Biology
Sunayana Dagar, Kumari Pushpa, Diksha Pathak, Sarbani Samaddar, Anjana Saxena, Sourav Banerjee, Sivaram V. S. Mylavarapu
Summary: This study demonstrates a novel mRNA-guided mechanism of TNT formation through the maintenance of cellular 14-3-3 zeta mRNA levels by the RBP nucleolin.
Review
Pharmacology & Pharmacy
F. Sanders Pair, Talene A. Yacoubian
Summary: 14-3-3 proteins are a family of proteins expressed throughout the body that are involved in various diseases. Despite the challenges in targeting their interactions, recent advances have made it possible to develop compounds that target 14-3-3 interactions with therapeutic implications for neurodegenerative disorders. Challenges still remain in optimizing specificity and target engagement to avoid unintended negative consequences.
TRENDS IN PHARMACOLOGICAL SCIENCES
(2021)
Article
Plant Sciences
Yuqing Zhu, Wei Kuang, Jun Leng, Xue Wang, Linlin Qiu, Xiangyue Kong, Yongzhang Wang, Qiang Zhao
Summary: Apple 14-3-3 proteins play an important role in salt tolerance by modulating the expression of salt stress-related genes. MdGRF6, a member of the Md14-3-3 gene family, was found to be involved in salt response. Overexpression of MdGRF6 in transgenic tobacco and apple calli resulted in decreased salt tolerance, while RNAi-mediated silencing of MdGRF6 improved salt stress tolerance. Furthermore, the expression levels of salt stress-related genes were more strongly down-regulated in MdGRF6-overexpressing apple calli.
FRONTIERS IN PLANT SCIENCE
(2023)
Article
Chemistry, Multidisciplinary
Subashini Mathivanan, Puneeth Kumar Chunchagatta Lakshman, Manvi Singh, Saranya Giridharan, Keerthana Sathish, A. Manjunath Hurakadli, Kavitha Bharatham, Neelagandan Kamariah
Summary: In this study, the interaction between FOXO3apS253 phosphopeptide and 14-3-36 was comprehensively analyzed using fluorescence polarization, isothermal titration, and molecular dynamics simulations. The high-resolution structure of the FOXO3apS253:14-3-36 complex revealed a distinct mode of interaction compared to other 14-3-3 phosphopeptide complexes. The study also identified structural differences between the binding of FOXO1pS256 and FOXO3apS253 to various 14-3-3 isoforms, providing a framework for the rational design of isoform-specific FOXO/14-3-3 protein-protein interaction inhibitors for therapy.
Article
Cell Biology
Indrajyoti Indra, Regina B. Troyanovsky, Kathleen J. Green, Sergey M. Troyanovsky
Summary: In this study, the role of the desmosomal ARM protein Pkp3 in integrating desmosomes into the apical cell junctional complex (AJC) was investigated using polarized DLD1 cells. The data suggest that Par3 facilitates DSM assembly within the AJC and controls the availability of Pkp3 in tricellular contacts, highlighting the importance of apical polarity proteins in desmosome localization.
MOLECULAR BIOLOGY OF THE CELL
(2021)
Review
Pharmacology & Pharmacy
Sathapana Kongsamut, Haifeng Eishingdrelo
Summary: The activation of G-protein-coupled receptors (GPCRs) triggers a cascade of reactions, including changes in receptor structures, phosphorylation, protein recruitment, trafficking and gene expression. Two well-studied signaling pathways of GPCRs are G-protein-mediated and arrestin-mediated pathways. Recently, interactions between GPCRs and 14-3-3 proteins have been discovered, which opens new possibilities in signal transduction. 14-3-3 proteins are crucial for GPCR trafficking and signal transduction, providing potential for studying GPCR function and therapeutics.
DRUG DISCOVERY TODAY
(2023)
Article
Chemistry, Multidisciplinary
Emira J. Visser, Priyadarshini Jaishankar, Eline Sijbesma, Marloes A. M. Pennings, Edmee M. F. Vandenboorn, Xavier Guillory, R. Jeffrey Neitz, John Morrow, Shubhankar Dutta, Adam R. Renslo, Luc Brunsveld, Michelle R. Arkin, Christian Ottmann
Summary: Small-molecule stabilization of protein-protein interactions (PPIs) is a promising strategy in chemical biology and drug discovery. In this study, a fragment-linking approach targeting the interface of 14-3-3 and a peptide derived from the estrogen receptor alpha (ERα) protein was developed. The initial hybrid molecule, supported by 20 crystal structures, was optimized to selectively stabilize the 14-3-3/ERα interaction by 25-fold. The high-resolution structures of the fragments, co-crystals, and linked fragments demonstrate a feasible strategy for developing orthosteric PPI stabilizers.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2023)
Review
Neurosciences
Meaghan Navarrete, Yi Zhou
Summary: Schizophrenia is a debilitating mental disorder with complex genetics. Evidence suggests a link between alterations in the 14-3-3 family and schizophrenia. Animal models allow for further exploration of this relationship and the study of schizophrenia pathology.
FRONTIERS IN MOLECULAR NEUROSCIENCE
(2022)
Article
Plant Sciences
Ningna Wang, Yiyuan Shi, Qun Jiang, Huan Li, Wenxia Fan, Yu Feng, Li Li, Bin Liu, Feng Lin, Wen Jing, Wenhua Zhang, Like Shen
Summary: In this study, the interaction between the 14-3-3 protein OsGF14b and the rice PI-PLC enzyme OsPLC1 was identified. It was found that OsGF14b can promote the activity and stability of OsPLC1, thereby improving rice salt tolerance.
PLANT CELL AND ENVIRONMENT
(2023)
Article
Biology
Sophie E. Ruff, Nikita Vasilyev, Evgeny Nudler, Susan K. Logan, Michael J. Garabedian
Summary: Ruff et al. demonstrate that PIM1 kinase phosphorylates androgen receptor (AR) and 14-3-3 zeta to coordinate their interaction at genes involved in cell migration and invasion, ultimately regulating the AR transcriptome in prostate cancer cells. The phosphorylation of AR and 14-3-3 zeta by PIM1 leads to their co-occupancy on chromatin and recruitment of additional co-regulatory proteins like hnRNPK and TRIM28, altering AR transcriptional activity. Overall, PIM1 phosphorylation of AR and 14-3-3 zeta is crucial for orchestrating their interaction and subsequent modulation of AR-dependent gene expression.
COMMUNICATIONS BIOLOGY
(2021)
Article
Dermatology
Katrin Rietscher, Annika Wolf, Gerd Hause, Annekatrin Rother, Rene Keil, Thomas M. Magin, Markus Glass, Carien M. Niessen, Mechthild Hatzfeld
JOURNAL OF INVESTIGATIVE DERMATOLOGY
(2016)
Article
Dermatology
Rene Keil, Katrin Rietscher, Mechthild Hatzfeld
JOURNAL OF INVESTIGATIVE DERMATOLOGY
(2016)
Article
Cell Biology
Annika Wolf, Katrin Rietscher, Markus Glass, Stefan Huettelmaier, Mike Schutkowski, Christian Ihling, Andrea Sinz, Aileen Wingenfeld, Andrej Mun, Mechthild Hatzfeld
JOURNAL OF CELL SCIENCE
(2013)
Article
Cell Biology
Lisa Mueller, Katrin Rietscher, Rene Keil, Marvin Neuholz, Mechthild Hatzfeld
JOURNAL OF CELL SCIENCE
(2020)
Editorial Material
Dermatology
Thomas M. Magin, Mechthild Hatzfeld
Summary: Single gene disorders are valuable for establishing genotype-phenotype correlations and understanding molecular mechanisms. Disease modifiers play a significant role in disease variability. A study on mutations in the DSG1 transmembrane domain reveals their impact on protein assembly and stability of desmosomes.
JOURNAL OF INVESTIGATIVE DERMATOLOGY
(2022)
Article
Dermatology
Katrin Rietscher, Heinz-Georg Jahnke, Matthias Ruebsam, Eric W. Lin, Cristina Has, M. Bishr Omary, Carien M. Niessen, Thomas M. Magin
Summary: This study demonstrates that the multikinase inhibitor PKC412 can reduce keratin aggregation in patient-derived EBS keratinocytes and restore intercellular adhesion. The findings provide a proof of concept for the repurposing of existing drugs for the targeted treatment of EBS and pave the way for clinical trials using PKC412 in EBS patients.
JOURNAL OF INVESTIGATIVE DERMATOLOGY
(2022)
Article
Cell Biology
Lisa Mueller, Rene Keil, Mechthild Hatzfeld
Summary: PKP3, an overexpressed component of desmosomes in cancer, controls the signaling axis from ERK to RB protein and E2F1 transcription factor, promoting cell cycle transition and proliferation.
Editorial Material
Biochemistry & Molecular Biology
Katrin Rietscher, Thomas M. Magin
Summary: A new study shows that laminin-111, as a component of the extracellular matrix, protects cell nuclei from actin-mediated forces by engaging the keratin cytoskeleton.