98%
921
2 minutes
20
RACGAP1 is a Rho-GTPase-activating protein originally discovered in male germ cells to inactivate Rac, RhoA and Cdc42 from the GTP-bound form to the GDP-bound form. GAP has traditionally been known as a tumor suppressor. However, studies increasingly suggest that overexpressed RACGAP1 activates Rac and RhoA in multiple cancers to mediate downstream oncogene overexpression by assisting in the nuclear translocation of signaling molecules and to promote cytokinesis by regulating the cytoskeleton or serving as a component of the central spindle. Contradictorily, it was also reported that RACGAP1 in gastric cancer could inactivate Rac and RhoA. In addition, studies have revealed that RACGAP1 can be a biomarker for prognosis, and its role in reducing doxorubicin sensitivity poses difficulties for treatment, while the current drug targets mainly focus on its downstream molecule. This article mainly reviews the expression regulation of RACGAP1 and its cancer-promoting functions through oncogene expression mediation and Rho-GTPase activation.
Download full-text PDF |
Source |
---|---|
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC11760467 | PMC |
http://dx.doi.org/10.3390/biom15010003 | DOI Listing |
Int J Mol Sci
May 2025
Department of Physiology, Faculty of Medical Sciences, University of Kragujevac, 34000 Kragujevac, Serbia.
The neurotrophic system includes neurotrophins, such as brain-derived neurotrophic factor (BDNF) and its precursor proBDNF, which play conflicting roles in neuronal survival and apoptosis, with their balance having a significant impact on neurodegenerative outcomes. While BDNF is widely acknowledged as a potent neurotrophin that promotes neuronal survival and differentiation, its precursor, proBDNF, has the opposite effect, promoting apoptosis and neuronal death. This review highlights the new and unique aspects of BDNF/proBDNF interaction in the modulation of neuronal apoptotic pathways in neurodegenerative disorders.
View Article and Find Full Text PDFEur J Med Genet
June 2025
Department of Pediatric Neurology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan.
Recurrent somatic mosaic pathogenic variants of RHOA have been observed in a newly identified neuroectodermal syndrome, Ectodermal Dysplasia with Facial Dysmorphism and Acral, Ocular, and Brain Anomalies, Somatic Mosaic [EDFAOB]. All 12 previously reported patients had somatic mosaicism for RHOA variants. Conversely, no patients with non-mosaic germline variants of RHOA have been reported.
View Article and Find Full Text PDFBiochem Biophys Res Commun
June 2025
Department of Biochemistry and Molecular Biology, Kobe University Graduate School of Medicine, Kobe, Hyogo, 650-0017, Japan; Biosignal Research Center, Kobe University, Kobe, Hyogo, 657-8501, Japan. Electronic address:
The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike protein has the ability to induce multinucleated syncytia via cell-cell fusion, which is thought to be related to the pathogenesis of the coronavirus disease 2019 (COVID-19). However, the mechanism by which spike protein regulates cell fusion remains unclear. Given the close correlation between cell-cell fusion and membrane protrusions, we investigated the role of membrane-proximal actin regulators in spike-induced cell fusion.
View Article and Find Full Text PDFNeurobiol Dis
July 2025
Department of Psychiatry, Translational Neuroscience Program, University of Pittsburgh School of Medicine, Pittsburgh, PA 15213, United States of America. Electronic address:
During adolescence, a critical developmental epoch coincident with the emergence of clinical symptoms of schizophrenia, cerebral cortical dendritic growth shifts from a rapid phase, reaching equilibrium. Oligodendrocyte Myelin Glycoprotein (OMGp) expression peaks during adolescence and has a known role in regulating dendritic stabilization. However, the precise signaling pathways transduced by OMGp are unknown.
View Article and Find Full Text PDFFront Cell Dev Biol
April 2025
Department of Physiology and Biophysics, University of Illinois at Chicago, Chicago, IL, United States.
We have established a novel and evolutionarily-conserved function for chloride intracellular channel proteins (CLICs) in regulating Rho/Rac GTPases downstream of G protein-coupled receptors (GPCRs). Endothelial CLIC1 and CLIC4 are rapidly and transiently re-localized from the cytoplasm to the plasma membrane in response to the GPCR ligand sphingosine-1-phosphate (S1P), and both CLICs are required to activate Rac1 in response to S1P, but how they perform this function remains unknown. Biochemical studies suggest that CLICs act as non-specific ion channels and/or as glutathione-S-transferases, dependent on N-terminal features, Here we investigate CLIC functional domains and membrane localization requirements for their function in S1P-mediated Rac1 signaling.
View Article and Find Full Text PDF