ARL4D Antibody
- Known as:
- ARL4D Antibody
- Catalog number:
- AF1103a
- Product Quantity:
- 0.1mg
- Category:
- -
- Supplier:
- Abgen
- Gene target:
- ARL4D Antibody
Related genes to: ARL4D Antibody
- Gene:
- ARL4D NIH gene
- Name:
- ADP ribosylation factor like GTPase 4D
- Previous symbol:
- ARF4L
- Synonyms:
- -
- Chromosome:
- 17q21.31
- Locus Type:
- gene with protein product
- Date approved:
- 1995-08-23
- Date modifiied:
- 2015-11-19
Related products to: ARL4D Antibody
Related articles to: ARL4D Antibody
- The high mortality rate of metastatic cutaneous melanoma (SKCM) remains a major challenge in clinical treatment. This study used single-cell RNA sequencing (scRNA-Seq) technology to compare the differences between metastatic and primary tumour cells. By manually annotating cell types, significant disparities in cell communication patterns and functional pathways between the two groups were identified. Combined with transcriptomic data, differential gene analysis was performed to screen out a core gene set associated with tumour metastasis. To achieve accurate prediction of tumour metastasis, this study innovatively constructed a binary classification algorithm (PSO-SVM) integrating particle swarm optimisation (PSO) and support vector machines (SVMs). This model optimises SVM parameters via the PSO algorithm, addressing the limitations of traditional machine learning models such as insufficient accuracy and poor generalization ability in tumour metastasis prediction. Verified by comparison with mainstream machine learning methods, the PSO-SVM model exhibited superior classification performance and successfully identified five key metastasis-related genes: SFN, S100A8, KLF5, ARL4D and TINCR. Furthermore, the expression differences of these genes in the metastatic group were verified at the single-cell level, clarifying their regulatory roles in different cell types and states. Through an innovative analytical strategy integrating single-cell and transcriptomic data, this study elucidated the core molecular mechanisms of SKCM metastasis and key regulatory pathways in the tumour microenvironment, providing potential biomarkers and therapeutic targets for the early diagnosis and targeted treatment of SKCM metastasis. This PSO-SVM-integrated analysis method also offers new insights for research on metastasis mechanisms of other cancers. - Source: PubMed
Liao ZhiweiChen WeimingHe YingdiZheng YichenChen XiaonanShen Han - Self-association by small GTPases on membrane is critical for their signaling output and cellular function. However, a mechanistic understanding of how membrane components regulate this process remains incompletely understood. Here, we show that phosphatidylinositol 4,5-bisphosphate [PI(4,5)P] promotes Arl4D self-association to potentiate downstream Pak1 signaling. We first show that Arl4D self-association is GTP-dependent and occurs at the plasma membrane. Fibronectin stimulation increases this self-association through two cooperative mechanisms: i) direct binding of PI(4,5)P by Arl4D via a conserved C-terminal polybasic motif, and ii) phosphorylation of Arl4D at Ser144 by its effector kinase Pak1. As a result, Arl4D membrane residency and protein stability are enhanced, with downstream signaling through Pak1 also amplified. Furthermore, pursuing structural prediction using AlphaFold, we generate an Arl4D mutant defective in self-association but retains GTP binding and membrane targeting, and find that this mutant fails to activate Pak1 for cell migration, while forced self-association of this mutant restores these downstream effects. Collectively, our findings reveal how an extracellular matrix cue leads to directional cell migration through Arl4D assembling into signaling-competent multimers at the plasma membrane, with cooperation between lipid recognition and kinase-mediated feedback playing critical roles. - Source: PubMed
Publication date: 2026/03/04
Chang Ting-WeiLee Fang-Jen S - ADP-ribosylation factor-like 4D (Arl4D), a Ras small GTPases superfamily member, plays crucial roles in membrane trafficking, cytoskeletal remodeling and cell migration. GDP-bound Arl4D has previously been shown to locate at the mitochondria and alter mitochondrial morphology and activity; however, how the nucleotide-binding state and mitochondrial targeting of Arl4D is regulated had remained unclear. We now discover that TBC1D15, a well-known Rab7 GTPase-activating protein (GAP), functions also as an Arl4D GAP to promote Arl4D mitochondrial targeting. We initially show that GDP-bound Arl4D translocates to the mitochondria under serum starvation and affects mitochondrial homeostasis. We also show that TBC1D15 interacts with Arl4D through the TBC domain and promotes GTP hydrolysis of Arl4D. Knockdown of TBC1D15 leads to an increase in Arl4D activity and decreased Arl4D mitochondrial translocation under serum starvation. These findings support the hypothesis that TBC1D15 acts as an Arl4D GAP and reveal a new role for this GAP in modulating mitochondrial homeostasis. - Source: PubMed
Publication date: 2026/03/12
Chen Chia-TangLiu Tsai-JungLin Shin-JinChang Ting-WeiLee Fang-Jen S - Activation of extracellular signal-regulated kinases 1 and 2 (Erk1/2; also known as MAPK3 and MAPK1, respectively) at the plasma membrane usually leads to their translocation to various intracellular sites, where scaffolding proteins mediate substrate targeting. However, in platelet-derived growth factor (PDGF)-induced signaling, Erk1/2 phosphorylate Pak1 to drive cell migration while remaining at the plasma membrane, raising the question of whether scaffolding proteins are required. Similarly, the small GTPase Arf-like protein 4D (Arl4D) promotes cell migration by recruiting Pak1 to the plasma membrane and facilitating its phosphorylation, although the mechanism linking recruitment to phosphorylation remains unclear. To address these questions, we show that Arl4D functions as a scaffolding protein by recruiting Erk1/2 and Pak1 to the plasma membrane, assembling them into a functional complex. This complex allows Erk1/2 to phosphorylate Pak1, supporting the role of the latter in cell migration. Our findings identify Arl4D as a novel regulator of Erk1/2, reveal a conserved role of scaffolding proteins in Erk1/2 substrate targeting, and uncover an unrecognized interplay among Arl4D, Erk1/2 and Pak1. These insights provide a deeper understanding of the molecular coordination underlying Pak1-mediated cell migration and its regulation by Erk1/2 and Arl4D. - Source: PubMed
Publication date: 2025/05/22
Chang Ting-WeiLin Ming-ChiehYu Chia-JungLee Fang-Jen S - Dynamic changes in DNA methylation are prevalent during the progression of breast cancer. However, critical alterations in aberrant methylation and gene expression patterns have not been thoroughly characterized. Here, we utilized guide positioning sequencing (GPS) to conduct whole-genome DNA methylation analysis in a unique human breast cancer progression model: MCF10 series of cell lines (representing benign/normal, atypical hyperplasia, and metastatic carcinoma). By integrating with mRNA-seq and matched clinical expression data from The Cancer Genome Atlas (TCGA) and the Gene Expression Omnibus (GEO), six representative methylation-related differentially expressed genes (mrDEGs) were identified, including CAVIN2, ARL4D, DUSP1, TENT5B, P3H2, and MMP28. To validate our findings, we independently developed and optimized the dCas9-DNMT3L-DNMT3A system, achieving a high efficiency with a 98% increase in methylation at specific sites. DNA methylation levels significantly increased for the six genes, with CAVIN2 at 67.75 ± 1.05%, ARL4D at 53.29 ± 6.32%, DUSP1 at 57.63 ± 8.46%, TENT5B at 44.00 ± 5.09%, P3H2 at 58.50 ± 3.90%, and MMP28 at 49.60 ± 5.84%. RT-qPCR confirmed an inverse correlation between increased DNA methylation and gene expression. Most importantly, we mimicked tumor progression in vitro, demonstrating that transcriptional silencing of the TENT5B promotes cell proliferation in MCF10A cells owing to the crosstalk between hypermethylation and histone deacetylation. This study unveils the practical implications of DNA methylation dynamics of mrDEGs in reshaping epigenomic features during breast cancer malignant progression through integrated data analysis of the methylome and transcriptome. The application of the CRISPR/dCas9-based methylation editing technique elucidates the regulatory mechanisms and functional roles of individual genes within the DNA methylation signature, providing valuable insights for understanding breast cancer pathogenesis and facilitating potential therapeutic approaches in epigenome editing for patients with breast cancer. - Source: PubMed
Publication date: 2025/01/21
Zhang BaolongLi JinYu Wenqiang