keyword
https://read.qxmd.com/read/38533085/membrane-trafficking-alterations-in-breast-cancer-progression
#1
REVIEW
Andreia Ferreira, Pedro Castanheira, Cristina Escrevente, Duarte C Barral, Teresa Barona
Breast cancer (BC) is the most common type of cancer in women, and remains one of the major causes of death in women worldwide. It is now well established that alterations in membrane trafficking are implicated in BC progression. Indeed, membrane trafficking pathways regulate BC cell proliferation, migration, invasion, and metastasis. The 22 members of the ADP-ribosylation factor (ARF) and the >60 members of the rat sarcoma (RAS)-related in brain (RAB) families of small GTP-binding proteins (GTPases), which belong to the RAS superfamily, are master regulators of membrane trafficking pathways...
2024: Frontiers in Cell and Developmental Biology
https://read.qxmd.com/read/38508314/mechanism-of-gtpase-activation-of-a-prokaryotic-small-ras-like-gtpase-mgla-by-an-asymmetrically-interacting-mglb-dimer
#2
JOURNAL ARTICLE
Sukanya Chakraborty, Manil Kanade, Pananghat Gayathri
Cell polarity oscillations in Myxococcus xanthus motility are driven by a prokaryotic small Ras-like GTPase, MglA, which switches from one cell pole to the other in response to extracellular signals. MglA dynamics is regulated by MglB, which functions both as a GAP (GTPase activating protein) and a GEF (guanine nucleotide exchange factor) for MglA. With an aim to dissect the asymmetric role of the two MglB protomers in the dual GAP and GEF activities, we generated a functional MglAB complex by co-expressing MglB with a linked construct of MglA and MglB...
March 18, 2024: Journal of Biological Chemistry
https://read.qxmd.com/read/38501608/cryo-em-of-the-nucleosome-core-particle-bound-to-ran-rcc1-reveals-a-dynamic-complex
#3
JOURNAL ARTICLE
Shuya Kate Huang, John L Rubinstein, Lewis E Kay
Ras-related nuclear protein (Ran) is a member of the Ras superfamily of small guanosine triphosphatases (GTPases) and a regulator of multiple cellular processes. In healthy cells, the GTP-bound form of Ran is concentrated at chromatin, creating a Ran•GTP gradient that provides the driving force for nucleocytoplasmic transport, mitotic spindle assembly, and nuclear envelope formation. The Ran•GTP gradient is maintained by the regulator of chromatin condensation 1 (RCC1), a guanine nucleotide exchange factor that accelerates GDP/GTP exchange in Ran...
March 19, 2024: Biochemistry
https://read.qxmd.com/read/38499108/dbl-family-rhogefs-in-cancer-different-roles-and-targeting-strategies
#4
REVIEW
Xin-Yi Chen, Ao-Yu Cheng, Zi-Ying Wang, Jin-Mei Jin, Jia-Yi Lin, Bei Wang, Ying-Yun Guan, Hao Zhang, Yi-Xin Jiang, Xin Luan, Li-Jun Zhang
Small Ras homologous guanosine triphosphatase (Rho GTPase) family proteins are highly associated with tumorigenesis and development. As intrinsic exchange activity regulators of Rho GTPases, Rho guanine nucleotide exchange factors (RhoGEFs) have been demonstrated to be closely involved in tumor development and received increasing attention. They mainly contain two families: the diffuse B-cell lymphoma (Dbl) family and the dedicator of cytokinesis (Dock) family. More and more emphasis has been paid to the Dbl family members for their abnormally high expression in various cancers and their correlation to poor prognosis...
March 16, 2024: Biochemical Pharmacology
https://read.qxmd.com/read/38482438/preliminary-exploration-of-the-potential-biological-functions-and-prognosis-values-of-rab4b-in-pan-cancer-combing-with-experimental-validation-in-blca
#5
JOURNAL ARTICLE
Kezhen Li, Shengsheng Liang, Hua Mi
BACKGROUND: Ras-related protein Rab-4B (RAB4B), a small GTPase in the RAS superfamily, is involved in glucose homeostasis, synaptic homeostasis, adaptive immunity, and other processes. RAB4B has also been implicated in tumorigenesis, and its dysregulation has been linked to cancer in multiple organs. However, the potential role of RAB4B in human pan-cancers remains unknown, and whether RAB4B is a predictive biomarker for cancer immunotherapy is yet to be explored. METHODS: In order to investigate the potential for RAB4B as a therapeutic agent in human pan-cancers and its predictive properties, firstly, relevant data were downloaded from pan-cancers databases...
February 29, 2024: Translational Cancer Research
https://read.qxmd.com/read/38481347/stat3-mediated-up-regulation-of-dab2-via-src-yap1-signaling-axis-promotes-helicobacter-pylori-driven-gastric-tumorigenesis
#6
JOURNAL ARTICLE
Yantao Duan, Pengfei Kong, Mingzhu Huang, Yonghao Yan, Yi Dou, Binhao Huang, Jing Guo, Wei Kang, Caixia Zhu, Yuyan Wang, Donglei Zhou, Qiliang Cai, Dazhi Xu
BACKGROUND: Helicobacter pylori (H pylori) infection is the primary cause of gastric cancer (GC). The role of Disabled-2 (DAB2) in GC remains largely unclear. This study aimed to investigate the role of DAB2 in H pylori-mediated gastric tumorigenesis. METHODS: We screened various datasets of GC to analyze DAB2 expression and cell signaling pathways. DAB2 expression was assessed in human GC tissue microarrays. H pylori infection in vivo and in vitro models were further explored...
March 13, 2024: Biomarker Research
https://read.qxmd.com/read/38474278/neuronal-protection-by-ha-ras-gtpase-signaling-through-selective-downregulation-of-plasmalemmal-voltage-dependent-anion-channel-1
#7
JOURNAL ARTICLE
Sebastian Neumann, Konstantin Kuteykin-Teplyakov, Rolf Heumann
The small GTPase RAS acts as a plasma membrane-anchored intracellular neurotrophin counteracting neuronal degeneration in the brain, but the underlying molecular mechanisms are largely unknown. In transgenic mice expressing constitutively activated V12-Ha-RAS selectively in neurons, proteome analysis uncovered a 70% decrease in voltage-dependent anion channel-1 (VDAC-1) in the cortex and hippocampus. We observed a corresponding reduction in the levels of mRNA splicing variant coding for plasma membrane-targeted VDAC-1 (pl-VDAC-1) while mRNA levels for mitochondrial membrane VDAC-1 (mt-VDAC-1) remained constant...
March 6, 2024: International Journal of Molecular Sciences
https://read.qxmd.com/read/38463630/interactions-between-ras-and-rap-signaling-pathways-during-neurodevelopment-in-health-and-disease
#8
REVIEW
Salvatore J Cherra, Reagan Lamb
The Ras family of small GTPases coordinates tissue development by modulating cell proliferation, cell-cell adhesion, and cellular morphology. Perturbations of any of these key steps alter nervous system development and are associated with neurological disorders. While the underlying causes are not known, genetic mutations in Ras and Rap GTPase signaling pathways have been identified in numerous neurodevelopmental disorders, including autism spectrum, neurofibromatosis, intellectual disability, epilepsy, and schizophrenia...
2024: Frontiers in Molecular Neuroscience
https://read.qxmd.com/read/38453353/effects-of-hindlimb-unloading-on-the-mevalonate-and-mechanistic-target-of-rapamycin-complex-1-signaling-pathways-in-a-fast-twitch-muscle-in-rats
#9
JOURNAL ARTICLE
Munehiro Uda, Toshinori Yoshihara, Noriko Ichinoseki-Sekine, Takeshi Baba
Fast-twitch muscles are less susceptible to disuse atrophy, activate the mechanistic target of rapamycin complex 1 (mTORC1) signaling pathway, and increase protein synthesis under prolonged muscle disuse conditions. However, the mechanism underlying prolonged muscle disuse-induced mTORC1 signaling activation remains unclear. The mevalonate pathway activates the mTORC1 signaling pathway via the prenylation and activation of Ras homolog enriched in brain (Rheb). Therefore, we investigated the effects of hindlimb unloading (HU) for 14 days on the mevalonate and mTORC1 signaling pathways in the plantaris muscle, a fast-twitch muscle, in adult male rats...
March 2024: Physiological Reports
https://read.qxmd.com/read/38438343/endothelial-cells-regulate-alveolar-morphogenesis-by-constructing-basement-membranes-acting-as-a-scaffold-for-myofibroblasts
#10
JOURNAL ARTICLE
Haruko Watanabe-Takano, Katsuhiro Kato, Eri Oguri-Nakamura, Tomohiro Ishii, Koji Kobayashi, Takahisa Murata, Koichiro Tsujikawa, Takaki Miyata, Yoshiaki Kubota, Yasuyuki Hanada, Koichi Nishiyama, Tetsuro Watabe, Reinhard Fässler, Hirotaka Ishii, Naoki Mochizuki, Shigetomo Fukuhara
Alveologenesis is a spatially coordinated morphogenetic event, during which alveolar myofibroblasts surround the terminal sacs constructed by epithelial cells and endothelial cells (ECs), then contract to form secondary septa to generate alveoli in the lungs. Recent studies have demonstrated the important role of alveolar ECs in this morphogenetic event. However, the mechanisms underlying EC-mediated alveologenesis remain unknown. Herein, we show that ECs regulate alveologenesis by constructing basement membranes (BMs) acting as a scaffold for myofibroblasts to induce septa formation through activating mechanical signaling...
March 4, 2024: Nature Communications
https://read.qxmd.com/read/38403351/-trametenolic-acid-inhibits-migration-and-invasion-of-hepatocellular-carcinoma-hepg2-2-15-cells-via-rhoc-rock1-pathway
#11
JOURNAL ARTICLE
Yu-Lian Wan, Jun-Zhi Wang, Yuan Yuan, Wang-Yang Ye, Hua-Li Li, Xiao-Lan Zhang, Hong-Qi Zhang, Li-E Li
This study investigated the effect of trametenolic acid(TA) on the migration and invasion of human hepatocellular carcinoma HepG2.2.15 cells by using Ras homolog gene family member C(RhoC) as the target and probed into the mechanism, aiming to provide a basis for the utilization of TA. The methyl thiazolyl tetrazolium(MTT) assay was employed to examine the proliferation of HepG2.2.15 cells exposed to TA, and scratch and Transwell assays to examine the cell migration and invasion. The pull down assay was employed to determine the impact of TA on RhoC GTPase activity...
January 2024: Zhongguo Zhong Yao za Zhi, Zhongguo Zhongyao Zazhi, China Journal of Chinese Materia Medica
https://read.qxmd.com/read/38395209/adapting-recombinant-bacterial-alkaline-phosphatase-for-nucleotide-exchange-of-small-gtpases
#12
JOURNAL ARTICLE
Peter Frank, Min Hong, Brianna Higgins, Shelley Perkins, Troy Taylor, Vanessa Wall, Matthew Drew, Timothy Waybright, William Gillette, Dominic Esposito, Simon Messing
The small GTPase Rat sarcoma virus proteins (RAS) are key regulators of cell growth and involved in 20-30% of cancers. RAS switches between its active state and inactive state via exchange of GTP (active) and GDP (inactive). Therefore, to study active protein, it needs to undergo nucleotide exchange to a non-hydrolysable GTP analog. Calf intestine alkaline phosphatase bound to agarose beads (CIP-agarose) is regularly used in a nucleotide exchange protocol to replace GDP with a non-hydrolysable analog. Due to pandemic supply problems and product shortages, we found the need for an alternative to this commercially available product...
February 21, 2024: Protein Expression and Purification
https://read.qxmd.com/read/38388830/the-cnk-hyp-scaffolding-complex-promotes-raf-activation-by-enhancing-ksr-mek-interaction
#13
JOURNAL ARTICLE
Pierre Maisonneuve, Malha Sahmi, Fanny Bergeron-Labrecque, Xianjie Iris Ma, Juliette Queguiner, Geneviève Arseneault, Martin Lefrançois, Igor Kurinov, Rémi Fronzes, Frank Sicheri, Marc Therrien
The RAS-MAPK pathway regulates cell proliferation, differentiation and survival, and its dysregulation is associated with cancer development. The pathway minimally comprises the small GTPase RAS and the kinases RAF, MEK and ERK. Activation of RAF by RAS is notoriously intricate and remains only partially understood. There are three RAF isoforms in mammals (ARAF, BRAF and CRAF) and two related pseudokinases (KSR1 and KSR2). RAS-mediated activation of RAF depends on an allosteric mechanism driven by the dimerization of its kinase domain...
February 22, 2024: Nature Structural & Molecular Biology
https://read.qxmd.com/read/38383288/the-ancestral-type-of-the-r-ras-protein-has-oncogenic-potential
#14
JOURNAL ARTICLE
Antea Talajić, Kristina Dominko, Marija Lončarić, Andreja Ambriović-Ristov, Helena Ćetković
BACKGROUND: The R-RAS2 is a small GTPase highly similar to classical RAS proteins at the regulatory and signaling levels. The high evolutionary conservation of R-RAS2, its links to basic cellular processes and its role in cancer, make R-RAS2 an interesting research topic. To elucidate the evolutionary history of R-RAS proteins, we investigated and compared structural and functional properties of ancestral type R-RAS protein with human R-RAS2. METHODS: Bioinformatics analysis were used to elucidate the evolution of R-RAS proteins...
February 21, 2024: Cellular & Molecular Biology Letters
https://read.qxmd.com/read/38366640/photocontrol-of-small-gtpase-ras-fused-with-a-photoresponsive-protein
#15
JOURNAL ARTICLE
Nobuyuki Nishibe, Shinsaku Maruta
The small GTPase Ras plays an important role in intracellular signal transduction and functions as a molecular switch. In this study, we used a photoresponsive protein as the molecular regulatory device to photoregulate Ras GTPase activity. Photo zipper (PZ), a variant of the photoresponsive protein Aureochrome1 developed by Hisatomi et al. (1-9) was incorporated into the C-terminus of Ras as a fusion protein. The three constructs of the Ras-PZ fusion protein had spacers of different lengths between Ras and PZ...
February 15, 2024: Journal of Biochemistry
https://read.qxmd.com/read/38351706/unraveling-the-significance-of-mg-2-dependency-and-nucleotide-binding-specificity-of-h-ras
#16
JOURNAL ARTICLE
Amol Tagad, G Naresh Patwari
RAS is a small GTPase and acts as a binary molecular switch; the transition from its active to inactive state plays a crucial role in various cell signaling processes. Molecular dynamics simulations at the atomistic level suggest that the absence of cofactor Mg2+ ion generally leads to pronounced structural changes in the Switch-I than Switch-II regions and assists GTP binding. The presence of the Mg2+ ion also restricts the rotation of ϒ phosphate and enhances the hydrolysis rate of GTP. Further, the simulations reveal that the stability of the protein is almost uncompromised when Mg2+ is replaced with Zn2+ and not the Ca2+ ion...
February 13, 2024: Journal of Physical Chemistry. B
https://read.qxmd.com/read/38338768/unraveling-the-role-of-ras-homolog-enriched-in-brain-rheb1-and-rheb2-bridging-neuronal-dynamics-and-cancer-pathogenesis-through-mechanistic-target-of-rapamycin-signaling
#17
REVIEW
Mostafizur Rahman, Tuan Minh Nguyen, Gi Jeong Lee, Boram Kim, Mi Kyung Park, Chang Hoon Lee
Ras homolog enriched in brain (Rheb1 and Rheb2), small GTPases, play a crucial role in regulating neuronal activity and have gained attention for their implications in cancer development, particularly in breast cancer. This study delves into the intricate connection between the multifaceted functions of Rheb1 in neurons and cancer, with a specific focus on the mTOR pathway. It aims to elucidate Rheb1's involvement in pivotal cellular processes such as proliferation, apoptosis resistance, migration, invasion, metastasis, and inflammatory responses while acknowledging that Rheb2 has not been extensively studied...
January 25, 2024: International Journal of Molecular Sciences
https://read.qxmd.com/read/38333672/preclinical-evaluation-of-crispr-based-therapies-for-noonan-syndrome-caused-by-deep-intronic-lztr1-variants
#18
JOURNAL ARTICLE
Carolin Knauer, Henrike Haltern, Eric Schoger, Sebastian Kügler, Lennart Roos, Laura C Zelarayán, Gerd Hasenfuss, Wolfram-Hubertus Zimmermann, Bernd Wollnik, Lukas Cyganek
Gene variants in LZTR1 are implicated to cause Noonan syndrome associated with a severe and early-onset hypertrophic cardiomyopathy. Mechanistically, LZTR1 deficiency results in accumulation of RAS GTPases and, as a consequence, in RAS-MAPK signaling hyperactivity, thereby causing the Noonan syndrome-associated phenotype. Despite its epidemiological relevance, pharmacological as well as invasive therapies remain limited. Here, personalized CRISPR-Cas9 gene therapies might offer a novel alternative for a curative treatment in this patient cohort...
March 12, 2024: Molecular Therapy. Nucleic Acids
https://read.qxmd.com/read/38310752/research-progress-on-small-molecule-inhibitors-targeting-kras-g12c-with-acrylamide-structure-and-the-strategies-for-solving-kras-inhibitor-resistance
#19
REVIEW
Zhiyan Jiang, Yan Li, Xin Zhou, Jie Wen, Pengwu Zheng, Wufu Zhu
KRAS (Kirsten-RAS) is a highly mutated gene in the RAS (rat sarcoma) gene family that acts as a critical switch in intracellular signaling pathways, regulating cell proliferation, differentiation, and survival. The continuous activation of KRAS protein resulting from mutations leads to the activation of multiple downstream signaling pathways, inducing the development of malignant tumors. Despite the significant role of KRAS in tumorigenesis, targeted drugs against KRAS gene mutations have failed, and KRAS was once considered an undruggable target...
February 15, 2024: Bioorganic & Medicinal Chemistry
https://read.qxmd.com/read/38295671/ras-superfamily-gtpases-and-signal-transduction-in-euglena-gracilis
#20
JOURNAL ARTICLE
Mark C Field
Biological complexity is challenging to define, but can be considered through one or more features, including overall genome size, number of genes, morphological features, multicellularity, number of life cycle stages and the ability to adapt to different environments. Euglena gracilis meets several of these criteria, with a large genome of ∼38,000 protein coding genes and a considerable ability to survive under many different conditions, some of which can be described as challenging or harsh. Potential molecular exemplars of complexity tying these aspects together are signalling pathways, including GTPases, kinases and ubiquitylation, which increase the functionality of the gene-encoded proteome manyfold...
January 28, 2024: Protist
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