Ask about this productRelated genes to: RAP1GAP Blocking Peptide
- Gene:
- RAP1GAP NIH gene
- Name:
- RAP1 GTPase activating protein
- Previous symbol:
- RAP1GA1
- Synonyms:
- KIAA0474, RAP1GAP1, RAP1GAPII
- Chromosome:
- 1p36.12
- Locus Type:
- gene with protein product
- Date approved:
- 1993-04-12
- Date modifiied:
- 2016-10-05
Related products to: RAP1GAP Blocking Peptide
Related articles to: RAP1GAP Blocking Peptide
- Colorectal cancer (CRC) is a leading cause of cancer-related mortality worldwide, yet the association between folic acid (FA) intake and CRC risk remains controversial. This study investigated the effects of varying dietary FA levels on colorectal carcinogenesis and the underlying mechanisms. BALB/c mice were fed diets containing FA at <0.1, 2.0, 6.0, 8.0, or 20.0 mg/kg for 14 weeks. After 4 weeks, colorectal tumorigenesis was induced using the azoxymethane/dextran sulfate sodium (AOM/DSS) protocol. Tumor multiplicity, maximum tumor diameter, tumor volume, colorectal length, histopathology, and cell proliferation were assessed. Mechanistic assessments included uracil misincorporation, thymidylate synthase (TS), telomere attrition, genome-wide DNA methylation, RAP1 signaling, immune-related markers, and inflammatory cytokines in colorectal tissues. Both FA deficiency (<0.1 mg/kg) and excess (8.0/20.0 mg/kg) increased colorectal tumor burden, with increased tumor number, larger maximum diameter, greater tumor volume, shortened colorectal length, and enhanced cell proliferation, whereas the 6.0 mg/kg diet group showed the lowest tumor burden. FA deficiency reduced TS expression, elevated deoxyuridine monophosphate (dUMP) levels, decreased deoxythymidine monophosphate (dTMP) levels, increased uracil misincorporation, and exacerbated telomere attrition, as evidenced by shortened telomeres and increased damage. In contrast, excessive FA intake induced Rap1 GTPase-activating protein () hypermethylation, reduced Rap1GAP expression, enhanced RAP1 activity, and upregulated programmed death-ligand 1 (PD-L1) and cytotoxic T-lymphocyte-associated protein 4 (CTLA4) expression. Dietary FA can exhibit a U-shaped association with colorectal carcinogenesis, with protective effects observed within an optimal range. FA deficiency and excess may drive tumor development through distinct molecular pathways involving uracil misincorporation-induced telomere attrition and DNA methylation-mediated immunosuppression, respectively. - Source: PubMed
Publication date: 2026/04/09
Ren QinghanMa YunfeiLi ZhenshuWu QiLi TongtongHe XinLi WenChen YongjieMa FeiYan JingHuang Guowei - To investigate the role of Rap1GAP in myocardial hypertrophy and fibrosis and its potential mechanism. In animal experiments, 20 cardiac-specific Rap1GAP knockout mice (Rap1GAP) and 20 Rap1GAP homozygous floxed mice (Rap1GAP), aged 6-8 weeks, were divided into four groups: Rap1GAP+saline group, Rap1GAP+saline group, Rap1GAP+AngⅡ group, and Rap1GAP+AngⅡ group. Echocardiography was used to assess cardiac function in each group. HE staining was performed to observe the overall structure and cellular morphology of myocardial tissue. Wheat germ agglutinin staining was used to measure the cross-sectional area of cardiomyocytes. Masson staining and Sirius red staining were employed for quantitative analysis of myocardial fibrosis levels and collagen proportion. Western blot was used to detect the protein expression levels of Rap1GAP, α-smooth muscle actin (α-SMA), atrial natriuretic peptide (ANP), β-myosin heavy chain (β-MHC), collagen type Ⅰ, collagen type Ⅲ, transforming growth factor-β1 (TGF-β1), phosphorylated extracellular regulated kinase (p-ERK), extracellular regulated kinase (ERK), phosphorylated c-Jun N-terminal kinase (p-JNK), c-Jun N-terminal kinase (JNK), phosphorylated p38 mitogen-activated protein kinase (p-p38), p38 mitogen-activated protein kinase (p38), phosphorylated nuclear factor κB (p-NF-κB), and nuclear factor κB (NF-κB) in myocardial tissue. In cell experiments, primary cardiomyocytes and cardiac fibroblasts were isolated from 1-3-day-old Wistar rat neonates. Rap1GAP expression was knocked down by transfecting Rap1GAP small interfering RNA (si-Rap1GAP), and cells were divided into si-control (negative control siRNA)+saline group, si-Rap1GAP+saline group, si-control+AngⅡ group, and si-Rap1GAP+AngⅡ group. Rap1GAP was overexpressed by infecting with Rap1GAP adenovirus (Ad-Rap1GAP), and cells were divided into Ad-GFP (GFP empty vector adenovirus)+saline group, Ad-Rap1GAP+saline group, Ad-GFP+AngⅡ group, and Ad-Rap1GAP+AngⅡ group. For inhibitor rescue experiments, cardiac fibroblasts infected with Ad-Rap1GAP or Ad-GFP were treated with 10 μmol/L p38 inhibitor (SB203580) or TGF-β1 inhibitor (pirfenidone), forming Ad-Rap1GAP+AngⅡ+SB203580 group, Ad-Rap1GAP+Ang+pirfenidone group, Ad-GFP+AngⅡ+SB203580 group and Ad-GFP+Ang+pirfenidone group. Immunofluorescence staining was used to detect the expression levels of Rap1GAP, α-SMA, and proliferating cell nuclear antigen (PCNA) in cells. Dihydroethidium staining was employed to measure reactive oxygen species (ROS) levels. Western blot was used to detect the expression levels of target proteins (consistent with animal experiments). In animal experiments, compared with the Rap1GAP+AngⅡ group, the Rap1GAP+AngⅡ group showed larger left ventricular end-diastolic diameter and left ventricular end-systolic diameter, while the cardiomyocyte surface area, myocardial fibrosis ratio and myocardial collagen volume ratio were smaller. Additionally, the expression levels of ANP, β-MHC, collagen type Ⅰ, collagen type Ⅲ, and α-SMA were lower (all <0.05). Proteomic analysis revealed differences in the protein expression profiles of myocardial tissue between the Rap1GAP+AngⅡ group and the Rap1GAP+AngⅡ group at biological process, cellular component, and molecular function. In cell experiments, compared with the si-Rap1GAP+AngⅡ group, the si-control+AngⅡ group exhibited larger cardiomyocyte cross-sectional area, as well as higher expression levels of ANP, β-MHC, collagen type Ⅰ, collagen type Ⅲ and α-SMA, and a higher proportion of PCNA-positive cells (all <0.05). Compared with the Ad-GFP+AngⅡ group, the Ad-Rap1GAP+AngⅡ group showed larger cardiomyocyte cross-sectional area, higher expression levels of the aforementioned proteins, and a higher proportion of PCNA-positive cells (all <0.05). Furthermore, the relative expression levels of p-ERK/ERK, p-JNK/JNK, p-p38/p38, p-NF-κB/NF-κB proteins, and ROS levels in cardiomyocytes or cardiac fibroblasts were higher in the si-control+AngⅡ group than in the si-Rap1GAP+AngⅡ group (all <0.05), while these indices were higher in the Ad-Rap1GAP+AngⅡ group than in the Ad-GFP+AngⅡ group (all <0.05). Meanwhile, the ROS level, proportion of PCNA-positive cells, and expression levels of TGF-β1, p-ERK/ERK, p-JNK/JNK, p-p38/p38, collagen type Ⅰ, collagen type Ⅲ, and α-SMA proteins in cardiac fibroblasts were lower in the Ad-GFP+Ang+SB203580 group than in the Ad-GFP+AngⅡ group (all <0.05). The same trend was observed in the Ad-GFP+AngⅡ+pirfenidone group, with all aforementioned indices lower than those in the Ad-GFP+AngⅡ group (all <0.05). Rap1GAP may mediate cardiomyocyte hypertrophy by regulating the mitogen-activated protein kinase signaling pathway and the expression of its downstream target NF-κB. Meanwhile, Rap1GAP may promote myocardial fibrosis by inducing ROS production and activating the TGF-β1/mitogen-activated protein kinase signaling pathway. - Source: PubMed
Li X YShan T TYao YZhang Y QZhao Z - To investigate the association and shared pathogenic mechanisms between systemic lupus erythematosus (SLE) and thyroid cancer (TC) using an integrative multi-omics framework. - Source: PubMed
Publication date: 2026/01/19
Sun QiChen HuixianLiu Shu - Melanoma is an aggressive skin cancer derived from melanocytes, known for its high metastatic potential and poor prognosis. Understanding the molecular mechanisms underlying melanoma progression could provide novel therapeutic targets for improving treatment outcomes. Our study aims to investigate the role of the RHO family GTPase RHOJ in melanoma progression and its regulation of cell adhesion, proliferation, and apoptosis through the Rap1 signaling pathway. - Source: PubMed
Publication date: 2025/08/21
He XiMa JieXia JialiGuan ZhiqiangJiang Guan - TDP-43 pathology is a defining pathological hallmark of multiple neurodegenerative diseases, including amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). A major feature of TDP-43 pathology is its nuclear depletion, leading to the aberrant inclusion of cryptic exons during RNA splicing. and have emerged as prominent TDP-43 splicing targets, but the broader impact of TDP-43-dependent cryptic splicing on neuronal function remains unclear. Here, we report new TDP-43 splicing targets critical for membrane excitability and synaptic function, including , , and . Using human stem cell-derived neurons, we show that TDP-43 reduction induces cryptic splicing and downregulation of these genes, resulting in impaired excitability and synaptic transmission. In postmortem brains from patients with FTD, these cryptic splicing events occur selectively in neurons with TDP-43 pathology. Importantly, suppressing individual cryptic splicing events using antisense oligonucleotides partially restores neuronal function, and combined targeting almost fully rescues the synaptic deficit caused by TDP-43 loss. Together, our findings provide evidence that cryptic splicing in these synaptic and membrane excitability genes is not only a downstream marker but instead a direct driver of neuronal dysfunction, establishing a mechanistic link between TDP-43 pathology and neurodegeneration in ALS and FTD. - Source: PubMed
Publication date: 2025/09/02
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