Aberrant signal transduction downstream of the Ras GTPase has a well-established role in tumorigenesis. Mutations that result in hyperactivation of Ras are responsible for a third of all human cancers. Hence, small molecule inhibitors of the Ras signal transduction cascade have been under intense focus as potential cancer treatments. In both invertebrate and mammalian models, emerging evidence has also implicated components of the Ras signaling pathway in aging and metabolic regulation. Here, I review the current evidence for Ras signaling in these newly discovered roles highlighting the interactions between the Ras pathway and other longevity assurance mechanisms. Defining the role of Ras signaling in maintaining age-related health may have important implications for the development of interventions that could not only increase lifespan but also delay the onset and/or progression of age-related functional decline.
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http://dx.doi.org/10.3233/NHA-160021 | DOI Listing |
Unlabelled: SYNGAP1 is a key Ras-GAP protein enriched at excitatory synapses, with mutations causing intellectual disability and epilepsy in humans. Recent studies have revealed that in addition to its role as a negative regulator of G-protein signaling through its GAP enzymatic activity, SYNGAP1 plays an important structural role through its interaction with post-synaptic density proteins. Here, we reveal that intrinsic excitability deficits and seizure phenotypes in heterozygous Syngap1 knockout (KO) mice are differentially dependent on Syngap1 GAP activity.
View Article and Find Full Text PDFBiochem Biophys Rep
March 2025
School of Biosciences and Technology, Vellore Institute of Technology, Vellore, India.
Ras gene is frequently mutated in cancer. Among different subtypes of Ras gene, K-Ras mutation occurs in nearly 30 % of human cancers. K-Ras mutation, specifically K-Ras (G12D) mutation is prevalent in cancers like lung, colon and pancreatic cancer.
View Article and Find Full Text PDFEur J Neurosci
January 2025
Pavlov Institute of Physiology RAS, Saint-Petersburg, Russia.
The "oblique effect" refers to the reduced visual performance for stimuli presented at oblique orientations compared to those at cardinal orientations. In the cortex, neurons that respond to specific orientations are organized into orientation columns. This raises the question: Are the orientation signals in the iso-orientation columns associated with cardinal orientations the same as those in the iso-orientation columns associated with oblique orientations, and is this signal influenced by experience? To explore this, iso-orientation columns in visual area 18 were examined using optical imaging techniques.
View Article and Find Full Text PDFFEBS Open Bio
January 2025
Clinical Measurement Sciences, Global Research & Development, EMD Serono, Billerica, MA, USA.
MAPK signaling activation is an important driver event in colorectal cancer (CRC) tumorigenesis that informs therapy selection, but detection by liquid biopsy can be challenging. We analyze real-world comprehensive genomic profiling (CGP) data to explore the landscape of alterations in BRAF or RAS in CRC patients (N = 51 982) and co-occurrence with other biomarkers. A pathogenic RAS or BRAF alteration was found in 63.
View Article and Find Full Text PDFActa Trop
January 2025
Institute of Cytology and Genetics, Siberian Branch of Russian Academy of Sciences (ICG SB RAS), 10 Akad. Lavrentiev Ave., Novosibirsk, 630090, Russia; Department of Natural Sciences, Novosibirsk State University, 2 Pirogova Str., Novosibirsk, 630090, Russia. Electronic address:
Cell models emulating an in vitro parasitic infection can greatly improve our understanding of helminthiases. Nonetheless, it remains challenging to select an appropriate in vitro model to study molecular pathogenesis of infections by trematodes having a complex life cycle. Therefore, adequate models are in high demand.
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