Rad17 (Phospho-Ser646) Polyclonal Antibody
- Known as:
- Rad17 (Phospho-Ser646) Polyclonal Antibody
- Catalog number:
- 12394
- Product Quantity:
- USD
- Category:
- -
- Supplier:
- Signalway
- Gene target:
- Rad17 (Phospho-Ser646) Polyclonal Antibody
Related genes to: Rad17 (Phospho-Ser646) Polyclonal Antibody
- Gene:
- RAD17 NIH gene
- Name:
- RAD17 checkpoint clamp loader component
- Previous symbol:
- -
- Synonyms:
- Rad24, RAD17Sp, CCYC
- Chromosome:
- 5q13.2
- Locus Type:
- gene with protein product
- Date approved:
- 1998-07-31
- Date modifiied:
- 2016-10-05
Related products to: Rad17 (Phospho-Ser646) Polyclonal Antibody
Related articles to: Rad17 (Phospho-Ser646) Polyclonal Antibody
- Activation of the ATR-dependent DNA damage response (ATR-DDR) is well characterized; however, the molecular mechanisms underlying its maintenance and inactivation remain largely elusive. Rhino is the least understood component of ATR-DDR. Structural modeling and binding free energy calculations revealed structural remodeling involving Rad17, Rad9-Hus1-Rad1 (9-1-1), and Rhino during ATR-DDR progression. Biochemical and computational analyses revealed the competitive binding of Rad17 and Rhino to the 9-1-1 complex, suggesting a structural transition from the Rad17-9-1-1 complex to the Rhino-9-1-1 complex. The presence of two conserved KYxxL+ motifs in Rhino suggests that it bridges the two 9-1-1 complexes. This enables the polymerization of multiple 9-1-1 complexes through Rhino and explains the long-standing discrepancy between the conventional model and experimental observations of Rad17 and Rad9 foci. Furthermore, structural analysis of the Rad9 C-terminal tail revealed its ability to compete with both Rhino and Rad17, leading to disassembly of the checkpoint complex and providing a mechanism for checkpoint inactivation. Quantum chemical calculations revealed comparable binding free energies for intermediate complexes. These observations suggest that the Rad17-9-1-1-Rhino complex undergoes energetically equivalent structural transitions, providing a mechanistic basis for the sequential progression of ATR-DDR. - Source: PubMed
Fukumoto YasunoriYuki RyuzaburoOgra Yasumitsu - Epidemiological and experimental evidence indicate that hyperglycemia, transient hyperinsulinemia and insulin-like growth factor-1 promote an aggressive phenotype of breast tumor cells during diabetes mellitus. The present study evaluated the effect of high glucose (HG) concentration (30 mmol/l) on cisplatin sensitivity and gene expression in MDA-MB-231 triple-negative breast cancer (TNBC)-derived cells. Cisplatin cytotoxicity was assessed by the MTT assay and was attenuated by HG. This effect was accompanied by reduced caspase-3 activation, indicating impaired apoptosis. Differentially expressed genes between HG and normal glucose (5.6 mmol/l) conditions were analyzed by microarray. The upregulation of tetraspanin 1 () and frizzled 3 () was validated by reverse transcription-quantitative PCR. HG promotes cisplatin chemoresistance by preventing apoptosis. Additionally, HG altered the expression of genes involved in glucose, glycerophospholipid, purine and pyrimidine metabolism. Regulatory pathways affected included Wnt/β-catenin, p53 network, NF-κB survival and DNA damage response. Candidate genes potentially associated with HG-induced chemoresistance included and . Survival analysis using the KM-Plotter platform revealed that and amphiregulin expression were significantly associated with poor prognosis. By contrast, amyloid precursor protein () and N-cadherin () showed non-significant trends. Coexpression analyses demonstrated that and were positively correlated with This suggests they may contribute to tumor aggressiveness as part of -driven regulatory networks, rather than as independent prognostic markers. Collectively, the present findings demonstrated that HG promotes cisplatin resistance and aggressive features in TNBC cells through multiple metabolic and signaling pathways. Notably, these include the Wnt/β-catenin axis. Candidate biomarkers with potential prognostic and therapeutic relevance in diabetic breast cancer (BC) were also identified. - Source: PubMed
Publication date: 2025/10/02
Viedma-Rodríguez Araceli RubíMartínez-Hernández María GuadalupeFlores-López Luis AntonioVelázquez-Flores Miguel ÁngelEsparza-Garrido Ruth RuizPrado-Baeza Javier RodrigoBaiza-Gutman Luis Arturo - Neuropilin-1 is henceforth a relevant target in cancer treatment; however, its way of action remains partly elusive, and the development of small inhibitory molecules is therefore required for its study. Here, we report that two small-sized neuropilin antagonists (NRPa-47 and NRPa-48), VEGF-A/NRP-1 binding inhibitors, are able to decrease VEGF-Rs phosphorylation and to modulate their downstream cascades in the triple-negative breast cancer cell line (MDA-MB-231). Nevertheless, NRPas exert a divergent pathway regulation of MAPK phosphorylation, such as JNK-1/-2/-3, ERK-1/-2, and p38β/γ/δ-kinases, as well as their respective downstream targets. However, NRPa-47 and NRPa-48 apply a common down-regulation of the p38α-kinase phosphorylation and their downstream targets, emphasising its central regulating role. More importantly, none of the 40 selected kinases, including SAPK2a/p38α, are affected in vitro by NRPas, strengthening their specificity. Taken together, NRPas induced cell death by the down-modulation of pro-apoptotic and anti-apoptotic proteins, cell death receptors and adaptors, heat shock proteins (HSP-27/-60/-70), cell cycle proteins (p21, p27, phospho-RAD17), and transcription factors (p53, HIF-1α). In conclusion, we showed for the first time how NRPas may alter tumour cell signalling and contribute to the down-modulation of the cancer therapeutic key factor p38α-kinase phosphorylation. Thus, the efficient association of NRPas and p38α-kinase inhibitor strengthened this hypothesis. - Source: PubMed
Publication date: 2025/03/27
Borriello LuciaJarray RafikaRignault-Bricard RachelMontes MatthieuLopez NicolasMaciel Thiago TrovatiHermine OlivierRaynaud FrançoiseDemange LucLepelletier Yves - In the original publication [...]. - Source: PubMed
Publication date: 2025/03/25
Valenti FabioSacconi AndreaGanci FedericaGrasso GiuseppeStrano SabrinaBlandino GiovanniDi Agostino Silvia - Breast cancer stem cells (BCSCs) are a rare cell population that is responsible for tumour initiation, metastasis and chemoresistance. Despite this, the mechanism by which BCSCs withstand genotoxic stress is largely unknown. Here, we uncover a pivotal role for the arginine methyltransferase PRMT5 in mediating BCSC chemoresistance by modulating DNA repair efficiency. Mechanistically, we identify PRMT5 as a major regulator of DNA damage response (DDR) gene splicing in BCSCs, particularly those integral to the Fanconi Anaemia and homologous recombination pathways, with PRMT5 inhibition synergising with chemotherapy to promote BCSC apoptosis. A comparison of BCSCs and their bulk cell progeny identified some shared (ATM, DDX11, EXO1, FAN1, SLX4) but many unique (ATR, RAD17, RAD51D, RUVBL1) PRMT5-dependent alternative DDR splicing events. Surprisingly, these skipped exons and retained intron events rarely lead to substantial gene expression repression, suggesting that PRMT5 inhibition predominantly results in nuclear detention of intron-containing transcripts and the production of non-canonical isoforms with compromised protein function. Since many genes within the same DDR pathway undergo deregulated splicing, this study thus reveals additional points of vulnerability and alternative combination drug strategies that could improve the therapeutic efficacy of PRMT5 inhibitors to promote BCSC eradication. - Source: PubMed
Publication date: 2024/12/18
Gillespie Matthew SChiang KellyRegan-Mochrie Gemma LChoi Soo-YounWard Ciara MSahay DebashishGarcia PalomaArnold RolandDavies Clare C