scholarly journals FRL, a Novel Formin-Related Protein, Binds to Rac and Regulates Cell Motility and Survival of Macrophages

2000 ◽  
Vol 20 (18) ◽  
pp. 6872-6881 ◽  
Author(s):  
Shinri Yayoshi-Yamamoto ◽  
Ichiro Taniuchi ◽  
Takeshi Watanabe
Keyword(s):  
Cell Death ◽  
Cell Adhesion ◽  
Bone Marrow Cells ◽  
Apoptotic Cell ◽  
Small Gtpases ◽  
Apoptotic Cell Death ◽  
Cell Adhesion And Migration ◽  
Rho Family ◽  
And Migration ◽  
Related Proteins

ABSTRACT We have isolated a cDNA, frl(formin-related gene in leukocytes), a novel mammalian member of the formin gene family. The frlcDNA encodes a 160-kDa protein, FRL, that possesses FH1, FH2, and FH3 domains that are well conserved among other Formin-related proteins. An FRL protein is mainly localized in the cytosol and is highly expressed in spleen, lymph node, and bone marrow cells. Formin-related genes and proteins have been reported to play crucial roles in morphogenesis, cell polarity, and cytokinesis through interaction with Rho family small GTPases. FRL binds to Rac at its N-terminal region including the FH3 domain and associates with profilin at the FH1 domain. In a macrophage cell line, P388D1, overexpression of a truncated form of FRL containing only the FH3 domain (FH3-FRL) strongly inhibited cell adhesion to fibronectin and migration upon stimulation with a chemokine. Moreover, expression of the truncated FH3-FRL protein resulted in apoptotic cell death of P388D1 cells, suggesting that the truncated FH3-FRL protein may interfere with signals of FRL. Overexpression in the P388D1 cells of full-length FRL or of the truncated protein containing the FH3 and FH1 domains, with simultaneous expression of the truncated FH3-FRL protein, blocked apoptotic cell death and inhibition of cell adhesion and migration. These results suggest that FRL may play a role in the control of reorganization of the actin cytoskeleton in association with Rac and also in the regulation of the signal for cell survival.

scholarly journals Cell Death Related Proteins Beyond Apoptosis in the CNS

2022 ◽  
Vol 9 ◽  
Author(s):  
Bazhena Bahatyrevich-Kharitonik ◽  
Rafael Medina-Guzman ◽  
Alicia Flores-Cortes ◽  
Marta García-Cruzado ◽  
Edel Kavanagh ◽  
...  
Keyword(s):  
Cell Death ◽  
Protein Function ◽  
Apoptotic Cell ◽  
Apoptotic Cell Death ◽  
Original Function ◽  
New Concepts ◽  
Cytoskeleton Reorganization ◽  
Caspase Substrates ◽  
Cell Death Signaling ◽  
Related Proteins

Cell death related (CDR) proteins are a diverse group of proteins whose original function was ascribed to apoptotic cell death signaling. Recently, descriptions of non-apoptotic functions for CDR proteins have increased. In this minireview, we comment on recent studies of CDR proteins outside the field of apoptosis in the CNS, encompassing areas such as the inflammasome and non-apoptotic cell death, cytoskeleton reorganization, synaptic plasticity, mitophagy, neurodegeneration and calcium signaling among others. Furthermore, we discuss the evolution of proteomic techniques used to predict caspase substrates that could potentially explain their non-apoptotic roles. Finally, we address new concepts in the field of non-apoptotic functions of CDR proteins that require further research such the effect of sexual dimorphism on non-apoptotic CDR protein function and the emergence of zymogen-specific caspase functions.

scholarly journals Rho family GTPase Chp/RhoV induces PC12 apoptotic cell death via JNK activation

Small GTPases ◽  
2011 ◽  
Vol 2 (1) ◽  
pp. 17-26 ◽  
Author(s):  
Mikhail V. Shepelev ◽  
Jonathan Chernoff ◽  
Igor V. Korobko
Keyword(s):  
Cell Death ◽  
Apoptotic Cell ◽  
Apoptotic Cell Death ◽  
Rho Family ◽  
Jnk Activation

scholarly journals Otoprotective Effect of 2,3,4′,5-Tetrahydroxystilbene-2-O-β-d-Glucoside on Gentamicin-Induced Apoptosis in Mouse Cochlear UB/OC-2 Cells

Molecules ◽  
2020 ◽  
Vol 25 (13) ◽  
pp. 3070
Author(s):  
Yu-Hsuan Wen ◽  
Jia-Ni Lin ◽  
Rong-Shuan Wu ◽  
Szu-Hui Yu ◽  
Chuan-Jen Hsu ◽  
...  
Keyword(s):  
Cell Death ◽  
Molecular Mechanisms ◽  
Apoptotic Cell ◽  
Therapeutic Option ◽  
Apoptotic Cell Death ◽  
Ros Generation ◽  
Sod Activity ◽  
Ldh Release ◽  
Induced Apoptosis ◽  
Related Proteins

Excessive levels of reactive oxygen species (ROS) lead to mitochondrial damage and apoptotic cell death in gentamicin-induced ototoxicity. 2,3,4’,5-Tetrahydroxystilbene-2-O-β-d-glucoside (THSG), a bioactive constituent, isolated from Polygonum multiflorum Thunb., exhibits numerous biological benefits in treating aging-related diseases by suppressing oxidative damage. However, its protective effect on gentamicin-induced ototoxicity remains unexplored. Therefore, here, we aimed to investigate the otoprotective effect of THSG on gentamicin-induced apoptosis in mouse cochlear UB/OC-2 cells. We evaluated the effect of gentamicin and THSG on the ROS level, superoxide dismutase (SOD) activity, mitochondrial membrane potential, nuclear condensation, and lactate dehydrogenase (LDH) release, and the expression of apoptosis-related proteins was assessed to understand the molecular mechanisms underlying its preventive effects. The findings demonstrated that gentamicin increased ROS generation, LDH release, and promoted apoptotic cell death in UB/OC-2 cells. However, THSG treatment reversed these effects by suppressing ROS production and downregulating the mitochondrial-dependent apoptotic pathway. Additionally, it increased the SOD activity, decreased the expression of apoptosis-related proteins, alleviated the levels of the apoptotic cells, and impaired cytotoxicity. To the best of our knowledge, this is the first study to demonstrate that THSG could be a potential therapeutic option to attenuate gentamicin-induced ototoxicity.

scholarly journals Rac1 Signaling Modulates BCL-6-Mediated Repression of Gene Transcription

2009 ◽  
Vol 29 (15) ◽  
pp. 4156-4166 ◽  
Author(s):  
Patrícia Barros ◽  
Peter Jordan ◽  
Paulo Matos
Keyword(s):  
Cell Adhesion ◽  
Gene Transcription ◽  
Transcriptional Repressor ◽  
Small Gtpases ◽  
Luciferase Reporter ◽  
Luciferase Reporter Construct ◽  
Kinase Activation ◽  
Cell Adhesion And Migration ◽  
And Migration ◽  
Species Production

ABSTRACT Rac1 is a member of the Rho family of small GTPases that not only regulates signaling pathways involved in cell adhesion and migration but also regulates gene transcription. Here we show that the transcriptional repressor BCL-6 is regulated by Rac1 signaling. Transfection of active Rac1 mutants into colorectal DLD-1 cells led to increased expression of a BCL-6-controlled luciferase reporter construct. Conversely, inhibition of endogenous Rac1 activation by the Rac1 inhibitor NSC23766 decreased reporter activity. Moreover, BCL-6 lost its typical localization to nuclear dots upon activation of Rac1 and became predominantly soluble in a non-chromatin-bound cell fraction. Rac1 signaling also regulated the expression of endogenous BCL-6-regulated genes, including the p50 precursor NF-κB1/p105 and the cell adhesion molecule CD44. Interestingly, these effects were not stimulated by the alternative splice variant Rac1b. The mechanism of BCL-6 inhibition does not involve formation of a stable Rac1/BCL-6 complex and is independent of Rac-induced reactive oxygen species production or Jun NH2-terminal kinase activation. We show that PAK1 mediates inhibition downstream of Rac and can directly phosphorylate BCL-6. Together, these data provide substantial evidence that Rac1 signaling inhibits the transcriptional repressor BCL-6 in colorectal cells and reveal a novel pathway that links Rac1 signaling to the regulation of gene transcription.

Zearalenone inhibits T cell chemotaxis by inhibiting cell adhesion and migration related proteins

2019 ◽  
Vol 175 ◽  
pp. 263-271 ◽  
Author(s):  
Guodong Cai ◽  
Shunye Pan ◽  
Nannan Feng ◽  
Hui Zou ◽  
Jianhong Gu ◽  
...  
Keyword(s):  
Cell Adhesion ◽  
T Cell ◽  
Cell Adhesion And Migration ◽  
And Migration ◽  
Related Proteins ◽  
Cell Chemotaxis
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