Ask about this productRelated genes to: ARL11 antibody
- Gene:
- ARL11 NIH gene
- Name:
- ADP ribosylation factor like GTPase 11
- Previous symbol:
- -
- Synonyms:
- ARLTS1, FLJ33930
- Chromosome:
- 13q14.2
- Locus Type:
- gene with protein product
- Date approved:
- 2004-02-05
- Date modifiied:
- 2017-11-27
Related products to: ARL11 antibody
Related articles to: ARL11 antibody
- Phospholipase D1 (PLD1) is a lipid metabolizing enzyme that produces phosphatidic acid (PA) and contributes to pathologies such as cancer, neurodegeneration, and cardiovascular diseases. PLD1 is known to be activated by Rho GTPases at a well defined site, and by ARF GTPases at a separate, poorly-defined site. Recently, the ARF-like GTPase 11 (ARL11) was identified as an activator of PLD1, but the mechanism by which ARL11 stimulates PLD1 activity remained unknown. Here, we use in vitro biochemical assays and structural predictions to provide insight into PLD1 activation by ARL11. We find that ARL11 must be loaded with GTP to stimulate PLD1, and corroborate that the loop within the catalytic domain of PLD1 is necessary for this stimulation. Leveraging AlphaFold 3, we predicted the structure of an ARL11-PLD1 complex. Point mutants of ARL11 at the predicted PLD1-ARL11 interface disrupted PLD1 stimulation, confirming the orientation of ARL11 in complex with PLD1. The N- and C-terminal ends of the PLD1-specific loop were predicted to be disordered in the absence of ARL11 but were predicted to adopt secondary structure elements that interact with ARL11 in the complex. Internal deletion mutants of PLD1 that retained these elements, but removed the remainder of the loop, were sufficient for ARL11 stimulation. Overall, these findings suggest that ARL11 interacts with PLD1 using three adjacent, biochemically distinct interfaces, and that the ends of PLD1's disordered loop form ordered structures to facilitate these interactions. Together this advances our structural understanding for the activation of PLD1 by the small GTPase ARL11. - Source: PubMed
Publication date: 2026/07/28
Marr Douglas JGao ShujuanFrohman Michael AAirola Michael V - Prostate cancer (PCa) progression and therapeutic resistance are largely driven by aberrant oncogenic signaling and an immunosuppressive microenvironment. Ginsenoside Rg3, a natural saponin from Panax ginseng, exhibits antitumor and immunomodulatory activity, but its therapeutic efficacy is limited when used as a monotherapy. Here, we investigated the synergistic potential of combining Rg3 with near-infrared (NIR) exposure in PCa. In PC-3 and DU145 cells, co-treatment with Rg3 and NIR synergistically inhibited proliferation, migration, and angiogenesis, while promoting apoptosis and reversal of epithelial-mesenchymal transition. Bioinformatic and molecular analyses identified the RAS/RAF/ERK pathway as a key target, with Rg3 showing a strong potential to interact with RAS and suppressing downstream phosphorylation of RAF and ERK; pharmacologic RAS activation partially reversed these effects. Beyond direct tumor inhibition, the combination also enhanced macrophage ARL11 expression and reprogrammed tumor-associated macrophages from an M2 to M1 phenotype through suppression of tumor RAS signaling. In xenograft models, Rg3 and NIR co-treatment markedly reduced tumor growth without systemic toxicity and increased M1 infiltration within tumor tissues. Collectively, these findings demonstrate that Rg3 combined with NIR exerts potent and safe antitumor activity by concurrently targeting tumor-intrinsic RAS/RAF/ERK signaling and ARL11-mediated immune reprogramming, offering a promising multimodal strategy for PCa therapy. - Source: PubMed
Publication date: 2026/02/23
Zhang HaipingChang YingFu QiangJin TiefengZhang SongnanZhang Meihua - Resistance to poly-(ADP)-ribose polymerase inhibitors (PARPi) remains a significant challenge in clinical practice, leading to treatment failure in many patients. It is crucial to better understand the molecular mechanisms that underlie PARPi resistance. In this study, utilizing a genome-wide CRISPR activation screen with olaparib, we identified ARL11 as a potential modulator of PARPi treatment response in BRCA-wild-type MDA-MB-231 cells. Mechanistically, ARL11 interacts with STING to enhance innate immunity and forms positive feedback with type I interferon (IFN) induction, which induces ARL11 up-regulation and contributes to resistance to PARPi therapy. Additionally, we observed that ARL11 interacts with the RUVBL1 and RUVBL2 (RUVBL1/2) complex, the key DNA double-strand repair proteins, facilitating DNA homologous recombination (HR) repair and significantly reducing PARPi-induced DNA double-strand damages. Clinical sample analysis reveals that the expression levels of ARL11 and RUVBL1/2 are significantly elevated in breast cancer patients compared to healthy controls. Collectively, our findings suggested that ARL11 and RUVBL1/2 may be promising therapeutic targets to sensitize breast cancer cells to PARPi therapy. - Source: PubMed
Publication date: 2025/03/23
Zhang TengjiangZhang YuanWang XuxiangHu HaitianLin Christopher GXu YaruZheng Hanqiu - Atherosclerosis (AS), an arterial vasculature disease, is characterized by abnormal lipid accumulation and inflammatory response. ADP ribosylation factor like GTPase 11 (ARL11) is linked to multifarious processes in cells. This study aims to clarify the underlying mechanism of ARL11 in AS. - Source: PubMed
Publication date: 2024/09/05
Zhen YanhuaYang JiaqiSong JiXing ZeyuZheng Jiahe - Spinal cord injury (SCI) is a severe central nervous system injury and microglia are major participants in neuroinflammation after injury. ADP-ribosylation factor-like GTPase 11 (ARL11) is a GTP-binding protein. Whether ARL11 is involved in the SCI progression is unknown. In the impactor-induced moderate SCI mouse model, ARL11 protein and mRNA expression were significantly increased in the injury site. LPS (100 ng/mL) and IFN-γ (20 ng/mL) were incubated with BV2 cells (immortalized mouse microglial cell line) to drive them into an M1-like phenotype. ARL11 up-regulation was also observed in activated microglia in SCI mice and LPS and IFN-γ treated BV2 cells. Basso Mouse Scale scores and inclined plate test revealed that ARL11 deletion promoted motor function recovery in SCI mice. Pathological examination showed ARL11 knockdown reduced spinal cord tissue damage, increased neuron numbers, and inhibited neuronal apoptosis in SCI mice. ARL11 knockdown notably inhibited IL-1β and IL-6 production in vivo and in vitro. Furthermore, ARL11 deletion significantly inhibited iNOS protein and mRNA expression in vivo and in vitro, and COX-2 expression in vivo. Mechanism studies revealed that ARL11 silencing decreased phosphorylated ERK1/2 protein expression. Additionally, ELF1 knockdown significantly inhibited ARL11 protein and mRNA expression in vitro. ELF1 acted as a transcription activator in regulating ARL11 expression by binding to the promoter. In conclusion, ARL11 knockdown protects neurons by inhibiting M1 microglia-induced neuroinflammation, thereby promoting motor functional recovery in SCI mice. This may occur in part under the regulation of ELF1. Our study provides a new molecular target for SCI treatment. - Source: PubMed
Publication date: 2024/09/20
Zhang HaocongXiang LiangbiYuan HongYu Hailong