Cdc42 N17 (Dominant Negative) Recombinant Adenovirus
- Known as:
- Cdc42 N17 (Dominant Negative) Recombinant Adenovirus
- Catalog number:
- ADV-153
- Product Quantity:
- 50
- Category:
- -
- Supplier:
- Cell Biolabs
- Gene target:
- Cdc42 N17 (Dominant Negative) Recombinant Adenovirus
Related genes to: Cdc42 N17 (Dominant Negative) Recombinant Adenovirus
- Gene:
- ARHGAP1 NIH gene
- Name:
- Rho GTPase activating protein 1
- Previous symbol:
- -
- Synonyms:
- RhoGAP, p50rhoGAP, CDC42GAP, Cdc42GAP
- Chromosome:
- 11p11.2
- Locus Type:
- gene with protein product
- Date approved:
- 1997-08-28
- Date modifiied:
- 2014-11-18
- Gene:
- CDC42 NIH gene
- Name:
- cell division cycle 42
- Previous symbol:
- -
- Synonyms:
- G25K, CDC42Hs
- Chromosome:
- 1p36.12
- Locus Type:
- gene with protein product
- Date approved:
- 1991-06-06
- Date modifiied:
- 2019-04-23
Related products to: Cdc42 N17 (Dominant Negative) Recombinant Adenovirus
Related articles to: Cdc42 N17 (Dominant Negative) Recombinant Adenovirus
- Breast cancer is the most prevalent cancer type in women worldwide. It proliferates rapidly and can metastasize into farther tissues at any stage due to the gradual invasiveness and motility of the tumor cells. These crucial properties are the outcome of the weakened intercellular adhesion, regulated by small guanosine triphosphatases (GTPases), which hydrolyze to the guanosine diphosphate (GDP)-bound conformation. We investigated the inactivating effect of on Rho GTPases involved signaling pathways after treatment with a high dose of doxorubicin. Label-free quantitative proteomic analysis of the proteome isolated from the MCF-7 breast cancer cell line, treated with 1 μM of doxorubicin, identified , , and GTPases that were inactivated by the protein. Upregulation of the GTPases involved in the transforming growth factor-beta (TGF-beta) signaling pathway initiated epithelial-mesenchymal transitions. These findings demonstrate a key role of the protein in the disruption of the cell adhesion and simultaneously allow for a better understanding of the molecular mechanism of the reduced cell adhesion leading to the subsequent metastasis. The conclusions of this study corroborate the hypothesis that chemotherapy with doxorubicin may increase the risk of metastases in drug-resistant breast cancer cells. - Source: PubMed
Publication date: 2023/07/12
Géci ImrichBober PeterFilová EvaAmler EvženSabo Ján - Alzheimer's disease, the most common cause of dementia, is a chronic degenerative disease with typical pathological features of extracellular senile plaques and intracellular neurofibrillary tangles and a significant decrease in the density of neuronal dendritic spines. Cdc42 is a member of the small G protein family that plays an important role in regulating synaptic plasticity and is regulated by Cdc42GAP, which switches Cdc42 from active GTP-bound to inactive GDP-bound states regulating downstream pathways via effector proteins. However, few studies have focused on Cdc42 in the progression of Alzheimer's disease. In a heterozygous Cdc42GAP mouse model that exhibited elevated Cdc42-GTPase activity accompanied by increased Cdc42-PAK1-cofilin signalling, we found impairments in cognitive behaviours, neuron senescence, synaptic loss with depolymerization of F-actin and the pathological phenotypes of Alzheimer's disease, including phosphorylated tau (p-T231, AT8), along with increased soluble and insoluble Aβ1-42 and Aβ1-40, which are consistent with typical Alzheimer's disease mice. Interestingly, these impairments increased significantly with age. Furthermore, the results of quantitative phosphoproteomic analysis of the hippocampus of 11-month-old GAP mice suggested that Cdc42GAP deficiency induces and accelerates Alzheimer's disease-like phenotypes through activation of GSK-3β by dephosphorylation at Ser9, Ser389 and/or phosphorylation at Tyr216. In addition, overexpression of dominant-negative Cdc42 in the primary hippocampal and cortical neurons of heterozygous Cdc42GAP mice reversed synaptic loss and tau hyperphosphorylation. Importantly, the Cdc42 signalling pathway, Aβ1-42, Aβ1-40 and GSK-3β activity were increased in the cortical sections of Alzheimer's disease patients compared with those in healthy controls. Together, these data indicated that Cdc42GAP is involved in regulating Alzheimer's disease-like phenotypes such as cognitive deficits, dendritic spine loss, phosphorylated tau (p-T231, AT8) and increased soluble and insoluble Aβ1-42 and Aβ1-40, possibly through the activation of GSK-3β, and these impairments increased significantly with age. Thus, we provide the first evidence that Cdc42 is involved in the progression of Alzheimer's disease-like phenotypes, which may provide new targets for Alzheimer's disease treatment. - Source: PubMed
Zhu MengjuanXiao BinXue TaoQin SifeiDing JiuyangWu YueTang QingqiuHuang MengfanZhao NaYe YingshanZhang YuningZhang BoyaLi JuanGuo FukunJiang YongZhang LinZhang Lu - Spatiotemporal regulation of signaling cascades is crucial for various biological pathways, under the control of a range of scaffolding proteins. The BNIP-2 and Cdc42GAP Homology (BCH) domain is a highly conserved module that targets small GTPases and their regulators. Proteins bearing BCH domains are key for driving cell elongation, retraction, membrane protrusion, and other aspects of active morphogenesis during cell migration, myoblast differentiation, and neuritogenesis. We previously showed that the BCH domain of p50RhoGAP (ARHGAP1) sequesters RhoA from inactivation by its adjacent GAP domain; however, the underlying molecular mechanism for RhoA inactivation by p50RhoGAP remains unknown. Here, we report the crystal structure of the BCH domain of p50RhoGAP and model the human p50RhoGAP BCH domain to understand its regulatory function using in vitro and cell line studies. We show that the BCH domain adopts an intertwined dimeric structure with asymmetric monomers and harbors a unique RhoA-binding loop and a lipid-binding pocket that anchors prenylated RhoA. Interestingly, the β5-strand of the BCH domain is involved in an intermolecular β-sheet, which is crucial for inhibition of the adjacent GAP domain. A destabilizing mutation in the β5-strand triggers the release of the GAP domain from autoinhibition. This renders p50RhoGAP active, thereby leading to RhoA inactivation and increased self-association of p50RhoGAP molecules via their BCH domains. Our results offer key insight into the concerted spatiotemporal regulation of Rho activity by BCH domain-containing proteins. - Source: PubMed
Chichili Vishnu Priyanka ReddyChew Ti WengShankar SrihariEr Shi YinChin Cheen FeiJobichen ChackoQiurong Pan CatherineZhou YitingYeong Foong MayLow Boon ChuanSivaraman J - Angio-associated migratory cell protein (AAMP) is considered a pro-tumor protein, which contributes to angiogenesis, proliferation, adhesion, and other biological activities. Although AAMP is known to facilitate the motility of breast cancer cells and smooth muscle cells by regulating ras homolog family member A (RHOA) activity, the function of AAMP in the metastasis of non-small cell lung cancer (NSCLC) cells still remains unknown. In the present study, AAMP was upregulated in non-small cell lung carcinoma, and was found to promote migration and invasion in NSCLC cells. Further experiments demonstrated that AAMP interacted with cell division cycle 42 (CDC42) and promoted its activation, resulting in the formation of cellular protrusions. Subsequently, we found that AAMP enhanced CDC42 activation by impairing the combination of rho GTPase activating protein 1 (ARHGAP1) and CDC42. Taken together, we revealed and elucidated the critical role of AAMP in the migration and invasion of NSCLC cells and presented a new potential target for lung cancer therapy. - Source: PubMed
Publication date: 2020/12/03
Yao ShunShi FeifeiMu NingLi XiaopengMa GuilinWang YingyingSun XiaoyangLiu XiangguoSu Ling - Ewing Sarcoma (ES) is a highly aggressive bone tumor with peak incidence in the adolescent population. It has a high propensity to metastasize, which is associated with dismal survival rates of approximately 25%. To further understand mechanisms of metastasis we investigated microRNA regulatory networks in ES. Our studies focused on miR-130b due to our analysis that enhanced expression of this microRNA has clinical relevance in multiple sarcomas, including ES. Our studies provide insights into a novel positive feedback network involving the direct regulation of miR-130b and activation of downstream signaling events contributing toward sarcoma metastasis. Specifically, we demonstrated miR-130b induces proliferation, invasion, and migration in vitro and increased metastatic potential in vivo. Using microarray analysis of ES cells with differential miR-130b expression we identified alterations in downstream signaling cascades including activation of the CDC42 pathway. We identified ARHGAP1, which is a negative regulator of CDC42, as a novel, direct target of miR-130b. In turn, downstream activation of PAK1 activated the JNK and AP-1 cascades and downstream transcriptional targets including IL-8, MMP1 and CCND1. Furthermore, chromatin immunoprecipitation of endogenous AP-1 in ES cells demonstrated direct binding to an upstream consensus binding site within the miR-130b promoter. Finally, small molecule inhibition of PAK1 blocked miR-130b activation of JNK and downstream AP-1 target genes, including primary miR-130b transcripts, and miR-130b oncogenic properties, thus identifying PAK1 as a novel therapeutic target for ES. Taken together, our findings identify and characterize a novel, targetable miR-130b regulatory network that promotes ES metastasis. - Source: PubMed
Publication date: 2017/08/08
Satterfield LauraShuck RyanKurenbekova LyazatAllen-Rhoades WendyEdwards DeanHuang ShixiaRajapakshe KimalCoarfa CristianDonehower Lawrence AYustein Jason T