Editorial Material
Hematology
Jan A. Burger
Summary: The study reveals that MARCKS protein is differentially expressed in patients with chronic lymphocytic leukemia based on the mutation status of IGHV, and its expression and phosphorylation are linked to CLL cell migration through key signaling pathways. The findings were also confirmed in samples from patients treated with the BTK inhibitor acalabrutinib.
Article
Biochemical Research Methods
Haixiang Zhang, Yinan Zheng, Lifang Hou, Cheng Zheng, Lei Liu
Summary: In this study, a novel method is introduced to identify potential mediators in high-dimensional Cox regression, with successful control of false discovery rate through data dimension reduction and multiple-testing procedure. Application to DNA methylation markers in lung cancer patients reveals two potential mediating epigenetic markers.
Article
Cell Biology
Hai-Liang Zhang, Bing-Xin Hu, Zhi-Ling Li, Tian Du, Jia-Lu Shan, Zhi-Peng Ye, Xiao-Dan Peng, Xuan Li, Yun Huang, Xian-Ying Zhu, Yu-Hong Chen, Gong-Kan Feng, Dajun Yang, Rong Deng, Xiao-Feng Zhu
Summary: Through CRISPR-Cas9 and kinase inhibitor screening, Zhang et al. found that PKC beta II phosphorylates and activates ACSL4 to enhance polyunsaturated fatty acid-containing lipid biosynthesis, thereby promoting accumulation of lipid peroxidation and ferroptosis.
NATURE CELL BIOLOGY
(2022)
Article
Chemistry, Multidisciplinary
Veronika M. Shoba, Dhanushka N. P. Munkanatta Godage, Santosh K. Chaudhary, Arghya Deb, Sachini U. Siriwardena, Amit Choudhary
Summary: Phosphorylation-inducing chimeric small molecules (PHICS) can enable protein kinase C (PKC) to have new activities, such as inducing inhibitory neo-phosphorylations on a variant and phosphorylating cytosol-based neo-substrates. PKC with PHICS can also induce death of chronic myeloid leukemia cells. Synthetic chemistry has the power to expand the chemical and functional diversity of proteins in cells using bifunctional molecules.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2022)
Article
Chemistry, Physical
Huan Liu, Xiuxia Su, Jing Zhang, Jia Xu, Dong Yang, Qingcai Chen
Summary: The study demonstrated a rapid PKC detection method based on liquid crystal biosensor and nano-modified signal amplification technology, achieving sensitive detection of PKC with good linear relationship and a very low detection limit in a wide linear range.
COLLOIDS AND SURFACES A-PHYSICOCHEMICAL AND ENGINEERING ASPECTS
(2021)
Article
Pharmacology & Pharmacy
Yao Chen, Bernardo L. Sabatini
Summary: In addition to inhibiting PKA activity, PKI was found to facilitate the activation of multiple isoforms of PKC at higher concentrations. This suggests the need for appropriate interpretation of experimental results when using PKI as a pharmaceutical agent. The study provides a foundation for exploring the potential functions of PKI in regulating PKC activity and coordinating PKC and PKA activities.
FRONTIERS IN PHARMACOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Juying Jiao, Linjie Ruan, Chien-shan Cheng, Fengjiao Wang, Peiwen Yang, Zhen Chen
Summary: In this study, aberrantly expressed kinases in pancreatic cancer (PC) were identified, and the role of RIPK2 kinase was validated in promoting cancer cell proliferation, migration, and invasion. RIPK2 knockout inhibited tumor growth and metastasis in PC, and also affected autophagosome formation, ROS production, and cell apoptosis. Additionally, the interaction between oncogenic kinase PRKCI and RIPK2 was found to enhance the downstream phosphorylation of NF-κB, JNK, and ERK.
MOLECULAR MEDICINE
(2023)
Article
Biochemistry & Molecular Biology
Jesus Bertran-Gonzalez, Caroline Dinale, Miriam Matamales
Summary: Multidisciplinary evidence suggests that the control of voluntary action is mediated by two major forms of behavioral processing: cognitively guided and autonomously guided. Brain-state irregularities, such as aging, often shift control towards the latter, but the neural mechanisms responsible are still unknown. By combining instrumental conditioning, cell-specific mapping, and chemogenetics, this study investigated strategies to enhance goal-directed control in aged mice. The findings suggest that desensitization of D2-SPN signaling in the striatum can shift behavior towards vigorous, goal-directed action and enhance cognitive functioning in habit-prone brains.
Article
Multidisciplinary Sciences
Yagmur Azbazdar, Nydia Tejeda-Munoz, Julia C. Monka, Alex Dayrit, Grace Binder, Gunes Ozhan, Edward M. De Robertis
Summary: Activation of Wnt signaling leads to macropinocytosis, which promotes tumor progression. Addition of the second messenger lipid sn-1,2 DAG induces macropinocytosis rapidly. Moreover, DAG addition enhances the effects of Wnt3a recombinant protein and GSK3 inhibitor LiCl in luciferase transcriptional reporter assays. In colorectal carcinoma cells with constitutive Wnt signaling, DAG addition increases nuclear beta-catenin levels, which can be partially inhibited by a macropinocytosis inhibitor. DAG also expands multivesicular bodies marked by CD63 protein. In vivo, microinjection of DAG induces Wnt-like twinned body axes in Xenopus embryos when co-injected with small amounts of LiCl.
Article
Biochemistry & Molecular Biology
Siwen Lyu, Qi Yang, Ting Li, Xuehui Duan, Jingbo Liu, Fengguang Pan, Yiding Yu, Ting Zhang
Summary: This research investigates the protective function of fermented egg-milk peptides (FEMPs) in inflammatory diseases and analyzes the potential targets and pathways regulated by digested FEMPs (dFEMPs). The results show that FEMPs can alleviate inflammatory symptoms, repair inflammation damage, and decrease pro-inflammatory cytokine levels. In silico experiments reveal that dFEMPs can influence multiple inflammation-related targets and signaling pathways. Molecular docking results indicate the importance of hydrogen-bonding and salt bridges in dFEMP-target interactions.
Review
Neurosciences
Rafael Falcon-Moya, Antonio Rodriguez-Moreno
Summary: Presynaptic kainate receptors modulate GABA and glutamate release in the central nervous system of mammals through both ionotropic and metabotropic actions. This biphasic modulation results in increased glutamate release at low KA concentrations and decreased neurotransmitter release at higher concentrations.
Article
Dermatology
Zhiping Wang, Yeon Jung Yoo, Rachel De La Torre, Christina Topham, Jon Hanifin, Eric Simpson, Robert O. Messing, Molly Kulesz-Martin, Yuangang Liu
Summary: TRIM32 deficiency enhances Th2 cell differentiation and is associated with atopic dermatitis. PKC is specifically ubiquitinated by TRIM32, influencing Th2 signaling regulation. High PKC and low TRIM32 levels are associated with the pathogenesis of AD.
JOURNAL OF INVESTIGATIVE DERMATOLOGY
(2021)
Article
Pharmacology & Pharmacy
Yiwei Shi, Rui Jiang, Xiaojiang Qin, Anqi Gao, Xiaomin Hou, Liangjing Chen, Xinrong Xu, Yunting Guo, Lina Chai, Liangyuan Zhao, Xuefeng Du, Furong Wu
Summary: This study investigated the role of nPKC in mediating PASMCs proliferation in PH. The findings revealed that hypoxia promoted PASMCs proliferation, with the most significant effect observed after 72 hours of treatment. The upregulation of PKC8 and PKC? expression under hypoxia led to PASMCs proliferation via the upregulation of AKT and ERK phosphorylation. These results suggest potential novel targets for molecular therapy of pulmonary hypertension.
EUROPEAN JOURNAL OF PHARMACOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Lina Lorenzen, Dennis Frank, Carsten Schwan, Robert Grosse
Summary: FMNL2 is upregulated in several cancers and plays important roles in cell migration, invasion, cell-cell adhesion and filopodia formation. Using structured illumination microscopy, it was found that FMNL2 promotes rapid and highly dynamic filopodia formation in epithelial cells while remaining on the tip of the growing filopodia. This filopodia tip localization depends on its N-terminal myristoylation and serine 1072 phosphorylation within the diaphanous-autoregulatory domain (DAD) by protein kinase C (PKC) alpha.
Editorial Material
Biochemistry & Molecular Biology
Daniel J. Dickinson
Summary: Animal cells establish polarity through the partitioning-defective protein system. The interactions between its four core proteins have been numerous, making it challenging to comprehend the organization and molecular mechanisms involved. In a recent JBC article, the Prehoda group successfully reconstituted some of these interactions in vitro, providing a clearer and simpler understanding of partitioning-defective complex assembly.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2023)
Article
Endocrinology & Metabolism
Jonas R. Knudsen, Kaspar W. Persson, Jaroslawna Meister, Christian S. Carl, Steffen H. Raun, Nicoline R. Andersen, Lykke Sylow, Bente Kiens, Thomas E. Jensen, Erik A. Richter, Maximilian Kleinert
Summary: This study found that the activity marker of mTORC2, p-NDRG1 Thr346, is a novel exercise-responsive protein in human skeletal muscle. Notably, contraction-induced p-NDRG1 Thr346 appears to require a systemic factor.
AMERICAN JOURNAL OF PHYSIOLOGY-ENDOCRINOLOGY AND METABOLISM
(2022)
Review
Endocrinology & Metabolism
Anders B. Klein, Maximilian Kleinert, Erik A. Richter, Christoffer Clemmensen
Summary: GDF15 is a ubiquitous cellular stress signal that can regulate appetite and metabolism to reduce body weight. Exercise can increase the levels of GDF15 and may have an impact on appetite and metabolism.
Article
Biotechnology & Applied Microbiology
Elise J. Needham, Janne R. Hingst, Benjamin L. Parker, Kaitlin R. Morrison, Guang Yang, Johan Onslev, Jonas M. Kristensen, Kurt Hojlund, Naomi X. Y. Ling, Jonathan S. Oakhill, Erik A. Richter, Bente Kiens, Janni Petersen, Christian Pehmoller, David E. James, Jorgen F. P. Wojtaszewski, Sean J. Humphrey
Summary: By combining experimental and computational analyses, personalized phosphoproteomics links signaling with biological function. This approach detects functionally relevant phosphorylation sites, revealing their roles in complex biology processes.
NATURE BIOTECHNOLOGY
(2022)
Article
Oncology
Kristin S. Inman, Yi Liu, Michele L. Scotti Buzhardt, Michael Leitges, Murli Krishna, Howard C. Crawford, Alan P. Fields, Nicole R. Murray
Summary: The protein kinase C iota (PKC iota) plays a promotive role in pancreatic cancer development, and inhibition of its expression prevents pancreatic cancer formation. It also affects the autophagy of pancreatic epithelial cells and the progression of pancreatic cancer.
Article
Public, Environmental & Occupational Health
Ryann L. Engle, Barbara G. Bokhour, Adam J. Rose, Joel I. Reisman, Guneet K. Jasuja
Summary: By studying six Veterans Affairs (VA) sites with varying levels of testosterone prescribing, we found that patient attitudes and beliefs towards testosterone did not differ across sites. Patients were the ones who usually initiated conversations about testosterone, not providers. We identified five key domains related to patient beliefs and provider perceived patient beliefs towards testosterone: reasons for initiation, information sources and expectations, receptivity towards discontinuation, patient/provider engagement, and patient self-advocacy in decision-making.
PATIENT EDUCATION AND COUNSELING
(2023)
Article
Nanoscience & Nanotechnology
Carmen Radeke, Raphael Pons, Marko Mihajlovic, Jonas R. Knudsen, Sarkhan Butdayev, Paul J. Kempen, Charis-Patricia Segeritz, Thomas L. Andresen, Christian K. Pehmoller, Thomas E. Jensen, Johan U. Lind
Summary: In order to achieve the automated fabrication of complex tissue mimicking constructs through 3D bioprinting, it is necessary to develop bioinks that are not only printable and biocompatible but also have integrated cell-instructive properties. Here, we present a scalable technique for generating nanofiber 3D printing inks with unique tissue-guiding capabilities. By tailoring the size and dispersibility of cellulose fibrils, we are able to create nanofibers that match the size and dimensions of natural collagen fibers, allowing for the orientation of cells and the spatial organization of engineered tissues during printing.
ACS APPLIED MATERIALS & INTERFACES
(2023)
Article
Education & Educational Research
Hagar Z. Pikkel Geva, Harel Gershgoren, Dana Nir, Maram Khazen, Adam J. Rose
Summary: Health-care professionals' hesitancy to be vaccinated during the COVID-19 crisis is influenced by factors such as sources of information, perceptions of vaccine necessity and risks, individual versus collective responsibility, and the political climate and media influence.
HEALTH EDUCATION RESEARCH
(2023)
Review
Oncology
Joan M. M. Marmol, Michala Carlsson, Steffen H. H. Raun, Mia K. K. Grand, Jonas Sorensen, Louise Lang Lehrskov, Erik A. A. Richter, Ole Norgaard, Lykke Sylow
Summary: Background: Insulin resistance is common in cancer patients and is associated with higher recurrence rates and reduced survival. However, it is unclear how frequently this condition occurs in patients with cancer. Methods: A systematic review and meta-analysis were conducted to assess insulin resistance in cancer patients. Fifteen studies were included, showing that cancer patients have significantly lower insulin-stimulated glucose disposal rates compared to control subjects. Interpretation: These findings highlight the importance of addressing insulin resistance in cancer patients to improve outcomes and patient care.
Article
Biology
Jonas R. Knudsen, Kaspar W. Persson, Carlos Henriquez-Olguin, Zhencheng Li, Nicolas Di Leo, Sofie A. Hesselager, Steffen H. Raun, Janne R. Hingst, Raphael Trouillon, Martin Wohlwend, Jorgen F. P. Wojtaszewski, Martin A. M. Gijs, Thomas Elbenhardt Jensen, Michael Czech
Summary: Microtubules play a crucial role in GLUT4 trafficking and maintaining an insulin-responsive GLUT4 pool in skeletal muscle fibers. Disruption of microtubules impairs long-range GLUT4 movement and decreases insulin-stimulated glucose uptake. Kinesin-1-mediated trafficking is essential for insulin-stimulated GLUT4 translocation and glucose uptake.
Article
Cell Biology
Kim A. Sjoberg, Casper M. Sigvardsen, Abdiel Alvarado-Diaz, Nicoline Resen Andersen, Mark Larance, Randy J. Seeley, Peter Schjerling, Jakob G. Knudsen, Georgios Katzilieris-Petras, Christoffer Clemmensen, Sebastian Beck Jorgensen, Katrien De Bock, Erik A. Richter
Summary: Growth differentiation factor 15 (GDF15) improves insulin action in obese rodents without weight loss by enhancing suppression of glucose production and increasing glucose uptake in adipose tissue and liver. This effect is mediated by GFRAL receptor and 0-adrenergic signaling. GDF15 also reduces glucagon levels independently of the GFRAL receptor.
Article
Neurosciences
Yann W. Yap, Patricia M. Rusu, Ashish Foollee, Adam J. Rose
Summary: We conducted a study on mice and found that dietary factors during the early life period from post-nursing to adulthood have lasting effects on traits in adulthood, particularly protein and fat intake. However, a standard diet in adulthood can quickly reverse the effects on body composition and glucose homeostasis from the early life diet. Nevertheless, some traits remain persistent, with low dietary protein levels in early life stably impacting lean and muscle mass, and early life dietary fat levels stably affecting serum and liver triglyceride levels.
JOURNAL OF PHYSIOLOGY-LONDON
(2023)
Article
Multidisciplinary Sciences
Lisbeth L. V. Moller, Mona S. Ali, Jonathan Davey, Steffen H. Raun, Nicoline R. Andersen, Jonathan Z. Long, Hongwei Qian, Jacob F. Jeppesen, Carlos Henriquez- Olguin, Emma Frank, Thomas E. Jensen, Kurt Hojlund, Jorgen F. P. Wojtaszewski, Joachim Nielsen, Tim T. Chiu, Mark P. Jedrychowski, Paul Gregorevic, Amira Klip, Erik A. Richter, Lykke Sylow
Summary: RhoGDIα is identified as a key regulator in controlling skeletal muscle insulin sensitivity by interacting with Rac1 and modulating GLUT4 translocation. Overexpression of RhoGDIα impairs insulin action and glucose tolerance, and elevated RhoGDIα protein content is observed in skeletal muscles of insulin-resistant patients with type 2 diabetes. This study highlights the clinical relevance of RhoGDIα as a controller of skeletal muscle insulin sensitivity and whole-body glucose homeostasis.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2023)
Article
Biochemistry & Molecular Biology
Carlos Henriquez-Olguin, Roberto Meneses-Valdes, Steffen H. Raun, Samantha Gallero, Jonas R. Knudsen, Zhencheng Li, Jingwen Li, Lykke Sylow, Enrique Jaimovich, Thomas E. Jensen
Summary: The study investigates the role of NOX2 in the interaction between diet-induced insulin resistance and exercise training in skeletal muscle. The results suggest that NOX2 deficiency worsens the effects of a high-fat diet on body weight, body composition, and glucose intolerance. Additionally, the lack of NOX2 activity during exercise training reduces several metabolic adaptations in skeletal muscle.
Article
Multidisciplinary Sciences
T. C. Phung Pham, Lucile Dollet, Mona S. Ali, Steffen H. Raun, Lisbeth L. V. Moller, Abbas Jafari, Nicholas Ditzel, Nicoline R. Andersen, Andreas M. Fritzen, Zachary Gerhart-Hines, Bente Kiens, Anu Suomalainen, Stephen J. Simpson, Morten Salling Olsen, Arnd Kieser, Peter Schjerling, Anni I. Nieminen, Erik A. Richter, Essi Havula, Lykke Sylow
Summary: Studies have found that the TNIK gene plays an important role in regulating lipid and glucose homeostasis in fruit flies and mice. Loss of the TNIK gene in fruit flies and mice resulted in changes in metabolite profiles and impaired lipogenesis. Additionally, TNIK gene variants were found to be associated with blood glucose, HbA1c, body mass index, body fat percentage, and feeding behavior.