| 2003 |
ARHGAP15 contains a pleckstrin homology (PH) domain, a RhoGAP domain, and a novel motif N-terminal to the GAP domain. The novel motif mediates nucleotide-independent Rac1 binding through the C-terminal half of Rac1 (established by swop mutants of Rac/Cdc42). The GAP domain shows specificity towards Rac1 in vitro. The PH domain is required for membrane/cell-periphery localization. Overexpression of full-length ARHGAP15 (but not PH-domain deletion mutant) increases actin stress fibers and cell contraction, effects attenuated by co-expression of dominant-negative Rac1(N17). ARHGAP15-expressing HeLa cells are resistant to phorbol myristate acetate treatment. |
In vitro GAP activity assay, Rac/Cdc42 swop mutants, overexpression/deletion constructs, co-expression with dominant-negative Rac1, cell morphology analysis, PMA treatment assay |
FEBS letters |
High |
12650940
|
| 2013 |
ARHGAP15 serves as a substrate of Rac effectors Pak1 and Pak2 (identified by protein microarray screen). ARHGAP15 also binds Pak1/2 via its PH domain. The ArhGAP15–Pak1/2 association results in mutual inhibition: ARHGAP15 GAP activity is inhibited and Pak1/2 kinase activity is inhibited. Knockdown of ARHGAP15 activates Pak1/2 both indirectly (through Rac activation) and directly (by disrupting the ARHGAP15/Pak complex), indicating a dual negative regulatory role. |
Protein microarray screen, co-immunoprecipitation, kinase activity assay, GAP activity assay, siRNA knockdown |
The Journal of biological chemistry |
High |
23760270
|
| 2016 |
Loss of ArhGAP15 in mice results in hyperactivation of Rac1/Rac3. In the hippocampus, ArhGAP15 knockout reduces the number of CR+, PV+, and SST+ inhibitory interneurons in CA3 and dentate gyrus due to reduced efficiency and directionality of their migration (pyramidal neurons are unaffected). Loss of ArhGAP15 alters neuritogenesis and the balance between excitatory and inhibitory synapses, resulting in increased spike frequency and bursts with poor synchronization. Adult ArhGAP15-/- mice show defective hippocampus-dependent working and associative memory. |
ArhGAP15 knockout mouse model, Rac1/Rac3 activity assays, interneuron counting and migration analysis, electrophysiology, behavioral testing |
Scientific reports |
High |
27713499
|
| 2017 |
FOXP3 transcriptionally regulates ARHGAP15 expression. Overexpression of FOXP3 upregulates ARHGAP15, which inactivates Rac1, inhibiting glioma cell migration. Silencing FOXP3 downregulates ARHGAP15 and activates Rac1, promoting migration. FOXP3 also regulates EMT markers E-cadherin and N-cadherin in this context. |
DNA microarray, qRT-PCR, Western blot, immunohistochemistry, overexpression and siRNA knockdown in glioma cells, migration assays |
Cancer science |
Medium |
27862679
|
| 2018 |
In colorectal cancer cells, ARHGAP15 overexpression activates PTEN signaling, increases FOXO1 activity, and decreases AKT phosphorylation. This leads to increased p21 (causing S-phase arrest), decreased MMP-2 and MMP-9 (reducing metastasis). Conversely, FOXO1 overexpression enhances ARHGAP15 expression and promoter activity, indicating a regulatory feedback loop. PTEN upregulation, FOXO1 overexpression, or AKT inhibition (MK2206) suppressed proliferation and metastasis in ARHGAP15-silenced cells. |
Overexpression and siRNA knockdown in CRC cell lines, Western blot, GSEA, luciferase promoter assay, in vivo xenograft/lung metastasis model, pharmacological AKT inhibition |
Cell death & disease |
Medium |
29867200
|
| 2018 |
ARHGAP15 overexpression suppresses cell proliferation and migration of breast cancer cell lines (MCF-7 and SK-BR-3). ARHGAP15 mRNA is induced by dihydrotestosterone, identifying it as an androgen-regulated gene, and its protein immunoreactivity positively correlates with Rac1 and androgen receptor expression in breast carcinoma tissues. |
Overexpression in breast cancer cell lines, proliferation and migration assays, dihydrotestosterone treatment, immunohistochemistry |
International journal of molecular sciences |
Medium |
29534468
|
| 2019 |
ARHGAP15 overexpression in lung cancer cells suppresses cell proliferation, migration, and invasion and reduces MMP-2, MMP-9, VEGF expression and STAT3 phosphorylation (p-STAT3). IL-6-induced proliferation and invasion are counteracted by ARHGAP15 upregulation. ARHGAP15 silencing-induced effects are inhibited by the STAT3 inhibitor AG490, placing ARHGAP15 upstream of STAT3 in this pathway. |
Overexpression and siRNA knockdown in lung cancer cell lines, proliferation/transwell assays, Western blot, pharmacological STAT3 inhibition (AG490) |
European review for medical and pharmacological sciences |
Medium |
31298335
|
| 2023 |
ARHGAP15 inactivates RAC1, thereby decreasing intracellular reactive oxygen species (ROS) accumulation, which enhances the antioxidant capacity and survival of gastric cancer cells under oxidative stress during metastatic colonization. This pro-colonization phenotype is phenocopied by RAC1 inhibition and rescued by constitutively active RAC1, placing ARHGAP15 upstream of RAC1 in the ROS-regulation pathway. |
Ectopic expression and genetic knockdown in gastric cancer cells, in vivo lung/lymph node colonization assay in mice, ROS measurement, RAC1 inhibition and constitutively active RAC1 rescue experiments |
PLoS genetics |
High |
36802400
|
| 2013 |
siRNA knockdown of ARHGAP15 in bovine fibroblast cells decreases the Bax/Bcl-2 ratio and caspase-3 levels in ethanol-treated cells, suggesting that ARHGAP15 activity is required for ethanol-induced apoptosis. Loss of ARHGAP15 is protective against ethanol-induced cell death. |
siRNA knockdown, RT-PCR, Western blot for Bax, Bcl-2, caspase-3, cell viability assay in ethanol-treated bovine fibroblasts |
Pakistan journal of pharmaceutical sciences |
Low |
23625437
|