Journal of Biological Chemistry最新文献

Loss of SLX4IP leads to Common Fragile Sites instability and compromises DNA interstrand crosslink repair in vivo. SLX4IP缺失导致共同脆弱位点不稳定，影响DNA链间交联修复。

IF 4.8 2区生物学

Journal of Biological Chemistry Pub Date : 2025-05-16 DOI: 10.1016/j.jbc.2025.110244

Andreas Ingham,Mukundhan Ramaswami,Ramanagouda Ramangoudr-Bhojappa,David Pladevall-Morera,Flavia De Santis,Javier Terriente,Ivan M Muñoz,John Rouse,Settara C Chandrasekharappa,Andres J Lopez-Contreras

{"title":"Loss of SLX4IP leads to Common Fragile Sites instability and compromises DNA interstrand crosslink repair in vivo.","authors":"Andreas Ingham,Mukundhan Ramaswami,Ramanagouda Ramangoudr-Bhojappa,David Pladevall-Morera,Flavia De Santis,Javier Terriente,Ivan M Muñoz,John Rouse,Settara C Chandrasekharappa,Andres J Lopez-Contreras","doi":"10.1016/j.jbc.2025.110244","DOIUrl":"https://doi.org/10.1016/j.jbc.2025.110244","url":null,"abstract":"Common Fragile Sites (CFSs) are chromosomal loci with inherent characteristics that make them difficult to fully replicate thus rendering them vulnerable to replication stress (RS). Under-replicated CFSs manifests as cytogenetic gaps and breaks on metaphase chromosomes. Moreover, CFSs are hotspots for tumorigenic chromosomal rearrangements. The Fanconi anemia (FA) pathway is at the core of a network of proteins that works to safeguard CFSs during replication and RS. Here, we uncover a novel role of SLX4IP in maintaining CFS stability. We show that SLX4IP localizes to stressed CFSs and that its loss exacerbates genome instability, including CFS expression. Furthermore, direct SLX4IP depletion leads to impaired replication and growth deficiencies. SLX4IP and FANCP/SLX4 are epistatic, suggesting that SLX4IP acts with SLX4 to maintain CFS stability. Finally, zebrafish larvae with homozygous knockout of slx4ip gene showed higher frequency of embryonic anomalies and sensitivity to DNA crosslinking agent, a typical cellular characteristic of FA patients. Our results establish a causal link between SLX4IP deficiency and chromosomal instability, which may explain how SLX4IP dysregulation contributes to cancer development.","PeriodicalId":15140,"journal":{"name":"Journal of Biological Chemistry","volume":"8 1","pages":"110244"},"PeriodicalIF":4.8,"publicationDate":"2025-05-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144087531","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Quantification and structure-function analysis of calpain-1 and calpain-2 protease subunit interactions. calpain-1和calpain-2蛋白酶亚基相互作用的定量和结构功能分析。

IF 4.8 2区生物学

Journal of Biological Chemistry Pub Date : 2025-05-16 DOI: 10.1016/j.jbc.2025.110243

Ivan Shapovalov,Prawin Rimal,Pitambar Poudel,Victoria Lewtas,Mathias Bell,Shailesh Kumar Panday,Brian J Laight,Danielle Harper,Stacy Grieve,George S Baillie,Kazem Nouri,Peter L Davies,Emil Alexov,Peter A Greer

{"title":"Quantification and structure-function analysis of calpain-1 and calpain-2 protease subunit interactions.","authors":"Ivan Shapovalov,Prawin Rimal,Pitambar Poudel,Victoria Lewtas,Mathias Bell,Shailesh Kumar Panday,Brian J Laight,Danielle Harper,Stacy Grieve,George S Baillie,Kazem Nouri,Peter L Davies,Emil Alexov,Peter A Greer","doi":"10.1016/j.jbc.2025.110243","DOIUrl":"https://doi.org/10.1016/j.jbc.2025.110243","url":null,"abstract":"Calpain-1 and calpain-2 are heterodimeric proteases consisting of a common small regulatory subunit CAPNS1 and a large catalytic subunit, CAPN1 or CAPN2, respectively. These calpains have emerged as potential therapeutic targets in cancer and other diseases through their roles in cell signaling pathways affecting sensitivity to chemotherapeutic and targeted drugs, and in promoting metastasis. While inhibition of calpains has the potential to provide therapeutic benefit to cancer patients, there are currently no clinically approved active site directed drugs that specifically and effectively inhibit them. However, the structures of calpain-1 and calpain-2 make them susceptible to allosteric inhibition aimed at interfering with heterodimerization of the catalytic and regulatory subunits, which is necessary for stability and proteolytic activity. Split-Nanoluciferase biosensors were generated to quantify the protein-protein interactions (PPIs) between the calcium-binding penta-EF hand (PEF) domains of CAPN1 or CAPN2 and CAPNS1. These biosensors were used to quantify the heterodimer dissociation constants (KD) of calpain-1 and calpain-2, estimated at 185 nM and 509 nM, respectively, in the presence of 5 mM Ca2+; and 362 nM and 1651 nM, respectively, in the presence of Mg2+. The half-maximal Ca2+ concentrations supporting these PPIs for calpain-1 and calpain-2 were 59.9 μM and 940.8 μM, respectively. Molecular modeling, based on the crystal structure of calpain-2, was used to predict 20 residues of the PEF domains that contribute to heterodimerization. Individual point mutation of CAPNS1 at Q263 reduced the catalytic activity of calpain-2 to 51.0 ± 6.4 % in live cells.","PeriodicalId":15140,"journal":{"name":"Journal of Biological Chemistry","volume":"14 1","pages":"110243"},"PeriodicalIF":4.8,"publicationDate":"2025-05-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144087532","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

LncRNA-induced lysosomal localization of NHE1 promotes increased lysosomal pH in macrophages leading to atherosclerosis. lncrna诱导的NHE1溶酶体定位促进巨噬细胞溶酶体pH升高，导致动脉粥样硬化。

IF 4.8 2区生物学

Journal of Biological Chemistry Pub Date : 2025-05-16 DOI: 10.1016/j.jbc.2025.110246

Pengcheng Shi,Bo Tang,Wen Xie,Ke Li,Di Guo,Yining Li,Yufeng Yao,Xiang Cheng,Chengqi Xu,Qing K Wang

{"title":"LncRNA-induced lysosomal localization of NHE1 promotes increased lysosomal pH in macrophages leading to atherosclerosis.","authors":"Pengcheng Shi,Bo Tang,Wen Xie,Ke Li,Di Guo,Yining Li,Yufeng Yao,Xiang Cheng,Chengqi Xu,Qing K Wang","doi":"10.1016/j.jbc.2025.110246","DOIUrl":"https://doi.org/10.1016/j.jbc.2025.110246","url":null,"abstract":"ANRIL, also referred to as CDKN2B-AS1, is a lncRNA gene implicated in the pathogenesis of multiple human diseases including atherosclerotic coronary artery disease, however, definitive in vivo evidence is lacking and the underlying molecular mechanism is largely unknown. In this study, we show that ANRIL overexpression causes atherosclerosis in vivo as transgenic mouse overexpression of full-length ANRIL (NR_003529) increases inflammation and aggravates atherosclerosis under ApoE-/- background (ApoE-/-ANRIL mice). Mechanistically, ANRIL reduces the expression of miR-181b-5p, which leads to increased TMEM106B expression. TMEM106B is significantly up-regulated in atherosclerotic lesions of both human CAD patients and ApoE-/-ANRIL mice. TMEM106B interacts and co-localizes with Na+-H+ exchanger NHE1, which results in mis-localization of NHE1 from cell membranes to lysosomal membranes, leading to increased lysosomal pH in macrophages. Large truncation and point mutation analyses define the critical amino acids for TMEM106B-NHE1 interaction and lysosomal pH regulation as F115 and F117 on TMEM106B and I537, C538, and G539 on NHE1. Topological analysis suggests that both N-terminus and C-terminus of NHE1 are located inside lysosomal lumen, and NHE1 is an important new proton efflux channel involved in raising lysosomal pH. A short TMEM106B peptide (YGRKKRRQRRR-L111A112V113F114F115L116F117) disrupting the TMEM106B-NHE1 interaction normalized lysosomal pH in macrophages with ANRIL overexpression. Our data demonstrate that ANRIL promotes atherosclerosis in vivo and identify the ANRIL/miR-181b-5p/TMEM106B-NHE1/lysosomal pH axis as the underlying molecular pathogenic mechanism for the chromosome 9p21.3 genetic locus for coronary artery disease.","PeriodicalId":15140,"journal":{"name":"Journal of Biological Chemistry","volume":"132 1","pages":"110246"},"PeriodicalIF":4.8,"publicationDate":"2025-05-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144087535","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Key Amino Acids in RNA Polymerase and Helicase Proteins Regulate RNA Synthesis Efficiency in Porcine Reproductive and Respiratory Syndrome Virus. 猪繁殖与呼吸综合征病毒RNA聚合酶和解旋酶蛋白关键氨基酸调控RNA合成效率

IF 4.8 2区生物学

Journal of Biological Chemistry Pub Date : 2025-05-16 DOI: 10.1016/j.jbc.2025.110247

Hui Li,Riteng Zhang,Honglin Xie,Yefei Zhou,Xinglong Wang

{"title":"Key Amino Acids in RNA Polymerase and Helicase Proteins Regulate RNA Synthesis Efficiency in Porcine Reproductive and Respiratory Syndrome Virus.","authors":"Hui Li,Riteng Zhang,Honglin Xie,Yefei Zhou,Xinglong Wang","doi":"10.1016/j.jbc.2025.110247","DOIUrl":"https://doi.org/10.1016/j.jbc.2025.110247","url":null,"abstract":"Porcine reproductive and respiratory syndrome virus (PRRSV) exhibits rapid evolution due to its high mutation rate and frequent recombination, posing significant challenges for disease control. In this study, we investigated the molecular mechanisms underlying strain-specific variations in PRRSV replication phenotypes. Using reverse genetics and molecular biology approaches, we established a non-infectious replicon model that simulates PRRSV genomic replication and subgenomic (sg) mRNA transcription at the cellular level. This model enabled the evaluation of regulatory effects of viral non-structural proteins (nsps) and transcription-regulating sequences (TRSs) on viral replication and transcription, revealing the crucial roles of nsp9 and nsp12 in RNA synthesis. Furthermore, we developed a subgenomic replicon system (sg-Rep-PRRSV) driven by a minimal replication-transcription complex (mini-RTC) to investigate the impact of specific mutations in PRRSV replicase-associated proteins on viral RNA synthesis efficiency. Our findings demonstrated that mini-RTC components derived from XM-2020 exhibited significantly higher transcriptional driving efficiency compared to those from GD strain (p < 0.01). Site-directed mutagenesis analysis identified critical amino acid residues contributing to differential RNA synthesis efficiency between strains: E141N, N416H, and S591A in nsp9, and S51D, L57T, and K349E in nsp10. These adaptive mutations likely modulate the catalytic conformations of RNA-dependent RNA polymerase (RdRp) and helicase, ultimately contributing to the distinct replication phenotypes observed among PRRSV strains. Our findings provide an insight into the molecular mechanisms underlying PRRSV evolution and adaptation, which have significant implications for mitigating future PRRS outbreak risks and maintaining sustainable development of the swine industry.","PeriodicalId":15140,"journal":{"name":"Journal of Biological Chemistry","volume":"17 1","pages":"110247"},"PeriodicalIF":4.8,"publicationDate":"2025-05-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144087534","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Circadian clock-independent ultradian rhythms in lipid metabolism in the Drosophila fat body. 果蝇脂肪体脂质代谢中不依赖生物钟的超昼夜节律。

IF 4.8 2区生物学

Journal of Biological Chemistry Pub Date : 2025-05-16 DOI: 10.1016/j.jbc.2025.110245

Blanca Lago Solis,Rafael Koch,Emi Nagoshi

引用次数: 0

The common yet enigmatic activity of histone tail clipping. 组蛋白剪尾的常见而神秘的活动。

IF 4.8 2区生物学

Journal of Biological Chemistry Pub Date : 2025-05-15 DOI: 10.1016/j.jbc.2025.110239

Elizabeth M Duncan

引用次数: 0

Machine Learning-Based Multimodal Radiomics and Transcriptomics Models for Predicting Radiotherapy Sensitivity and Prognosis in Esophageal Cancer. 基于机器学习的多模态放射组学和转录组学模型预测食管癌放疗敏感性和预后。

IF 4.8 2区生物学

Journal of Biological Chemistry Pub Date : 2025-05-15 DOI: 10.1016/j.jbc.2025.110242

Chengyu Ye,Hao Zhang,Zhou Chi,Zhina Xu,Yujie Cai,Yajing Xu,Xiangmin Tong

{"title":"Machine Learning-Based Multimodal Radiomics and Transcriptomics Models for Predicting Radiotherapy Sensitivity and Prognosis in Esophageal Cancer.","authors":"Chengyu Ye,Hao Zhang,Zhou Chi,Zhina Xu,Yujie Cai,Yajing Xu,Xiangmin Tong","doi":"10.1016/j.jbc.2025.110242","DOIUrl":"https://doi.org/10.1016/j.jbc.2025.110242","url":null,"abstract":"Radiotherapy plays a critical role in treating esophageal cancer, but individual responses vary significantly, impacting patient outcomes. This study integrates machine learning-driven multimodal radiomics and transcriptomics to develop predictive models for radiotherapy sensitivity and prognosis in esophageal cancer. We applied the SEResNet101 deep learning model to imaging and transcriptomic data from the UCSC Xena and TCGA databases, identifying prognosis-associated genes such as STUB1, PEX12, and HEXIM2. Using Lasso regression and Cox analysis, we constructed a prognostic risk model that accurately stratifies patients based on survival probability. Notably, STUB1, an E3 ubiquitin ligase, enhances radiotherapy sensitivity by promoting the ubiquitination and degradation of SRC, a key oncogenic protein. In vitro and in vivo experiments confirmed that STUB1 overexpression or SRC silencing significantly improves radiotherapy response in esophageal cancer models. These findings highlight the predictive power of multimodal data integration for individualized radiotherapy planning and underscore STUB1 as a promising therapeutic target for enhancing radiotherapy efficacy in esophageal cancer.","PeriodicalId":15140,"journal":{"name":"Journal of Biological Chemistry","volume":"30 1","pages":"110242"},"PeriodicalIF":4.8,"publicationDate":"2025-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144087526","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Damage-Associated Molecular Patterns (DAMPs) In Vascular Diseases. 血管疾病中损伤相关分子模式（DAMPs）

IF 4.8 2区生物学

Journal of Biological Chemistry Pub Date : 2025-05-15 DOI: 10.1016/j.jbc.2025.110241

Jacob Antonello,Partha Roy

{"title":"Damage-Associated Molecular Patterns (DAMPs) In Vascular Diseases.","authors":"Jacob Antonello,Partha Roy","doi":"10.1016/j.jbc.2025.110241","DOIUrl":"https://doi.org/10.1016/j.jbc.2025.110241","url":null,"abstract":"Research into the role of chronic sterile inflammation (i.e. a prolonged inflammatory state not caused by an infectious agent), in vascular disease progression has continued to grow over the last few decades. DAMPs have a critical role in this research due to their ability to link stress-causing cardiovascular risk factors to inflammatory phenotypes seen in vascular disease. In this mini-review, we will briefly summarize the DAMPs and receptor signaling pathways that have been extensively studied in the context of vascular disease, including TLRs, RAGE, cGAS-STING, and the NLRP3 inflammasome. In particular, we will discuss how these pathways can promote the release of pro-inflammatory cytokines and chemokines as well as vascular remodeling. Next, we will summarize the results of studies which have linked the various pro-inflammatory effects of DAMPs with the phenotypes in the context of vascular diseases including atherosclerosis, fibrosis, aneurysm, ischemia, and hypertension. Finally, we will discuss some pre-clinical and clinical trials that have targeted DAMPs, their receptors, or the products of their signaling pathways, and discuss the outlook and future directions for the field at large.","PeriodicalId":15140,"journal":{"name":"Journal of Biological Chemistry","volume":"126 1","pages":"110241"},"PeriodicalIF":4.8,"publicationDate":"2025-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144087536","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Blockade of the estrogen receptor alpha-pregnane X receptor axis protects ovariectomized mice against ethanol-induced hepatotoxicity. 阻断雌激素受体-孕烷X受体轴可保护去卵巢小鼠免受乙醇诱导的肝毒性。

IF 4.8 2区生物学

Journal of Biological Chemistry Pub Date : 2025-05-15 DOI: 10.1016/j.jbc.2025.110238

Elizabeth Twum,Malvin Ofosu-Boateng,Daniel O Nnamani,Lidya H Gebreyesus,Nour Yadak,Kusum K Kharbanda,Frank J Gonzalez,Maxwell A Gyamfi

{"title":"Blockade of the estrogen receptor alpha-pregnane X receptor axis protects ovariectomized mice against ethanol-induced hepatotoxicity.","authors":"Elizabeth Twum,Malvin Ofosu-Boateng,Daniel O Nnamani,Lidya H Gebreyesus,Nour Yadak,Kusum K Kharbanda,Frank J Gonzalez,Maxwell A Gyamfi","doi":"10.1016/j.jbc.2025.110238","DOIUrl":"https://doi.org/10.1016/j.jbc.2025.110238","url":null,"abstract":"Women develop alcohol-associated liver disease (ALD) faster than men at any level of alcohol consumption, implicating estrogen as a contributing factor. However, the precise mechanism remains unknown. Therefore, 12-weeks-old female C57BL/6N mice were subjected to either bilateral ovariectomy (OVX) or sham surgery. After a three-week recovery period, the mice were fed either a 5% ethanol (EtOH)-containing liquid diet or paired-fed control diet for 10 days followed by a single gavage dose of EtOH (5 g/kg, 30% EtOH solution). The mice were examined for serum biochemical parameters, hepatotoxicity, histology, expression of xenobiotic nuclear receptors PXR and CAR, and their target gene mRNAs and proteins in hepatic and perigonadal white adipose tissues (pgWAT). While OVX mice on a control diet significantly gained weight, EtOH significantly increased hepatotoxicity, residual EtOH levels, lipid peroxidation, and oxidative stress in sham-operated mice but not in their OVX counterparts. Additionally, in the livers and pgWAT of the sham mice, EtOH significantly increased the mRNA and/or protein levels of the major estrogen receptor ERα, PXR, CAR, and their target genes, proinflammatory cytokines and chemokines, lipogenic genes, and FGF21 levels, a predictive biomarker for ALD severity in humans, but inhibited NRF2 and its targets genes encoding NQO1 and BHMT. Unexpectedly, all these changes were attenuated in the EtOH-fed OVX mice by the upregulation of NRF2 and aryl hydrocarbon receptor (AhR) and their downstream antioxidant target genes. Together these results suggest the existence of an estrogen-regulated ERα-PXR-NRF2-signaling axis in liver and pgWAT which contributes to sexual dimorphism in ALD.","PeriodicalId":15140,"journal":{"name":"Journal of Biological Chemistry","volume":"42 1","pages":"110238"},"PeriodicalIF":4.8,"publicationDate":"2025-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144087537","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

The neural stem cell gene PAFAH1B1 controls cell cycle progression, DNA integrity, and paclitaxel sensitivity of triple-negative breast cancer cells. 神经干细胞基因PAFAH1B1控制三阴性乳腺癌细胞的细胞周期进程、DNA完整性和紫杉醇敏感性。

IF 4.8 2区生物学

Journal of Biological Chemistry Pub Date : 2025-05-14 DOI: 10.1016/j.jbc.2025.110235

Parth R Majmudar,Ruth A Keri

{"title":"The neural stem cell gene PAFAH1B1 controls cell cycle progression, DNA integrity, and paclitaxel sensitivity of triple-negative breast cancer cells.","authors":"Parth R Majmudar,Ruth A Keri","doi":"10.1016/j.jbc.2025.110235","DOIUrl":"https://doi.org/10.1016/j.jbc.2025.110235","url":null,"abstract":"Triple-negative breast cancer (TNBC) is a highly aggressive disease with limited approved therapeutic options. The rapid growth and genomic instability of TNBC cells makes mitosis a compelling target, and a current mainstay of treatment is paclitaxel (Ptx), a taxane that stabilizes microtubules during mitosis. While initially effective, acquired resistance to Ptx is common, and other antimitotic therapies can be similarly rendered ineffective due to the development of resistance or systemic toxicity underscoring the need for new therapeutic approaches. Interrogating CRISPR essentiality screens in TNBC cell lines, we identified PAFAH1B1 (LIS1) as a potential vulnerability in this disease. PAFAH1B1 regulates mitotic spindle orientation, proliferation, and cell migration during neurodevelopment, yet little is known regarding its function in breast cancer. We found that suppressing PAFAH1B1 expression in TNBC cells reduces cell number, while non-malignant cells remain unaffected. PAFAH1B1 suppression alters cell cycle dynamics, increasing mitotic duration and accumulation of cells in the G2/M phase. The suppression of PAFAH1B1 expression also increases DNA double-strand breaks, indicating a requirement for sustained PAFAH1B1 expression to maintain the genomic integrity of TNBC cells. Lastly, PAFAH1B1 silencing substantially enhances these defects in cells that are taxane-resistant and sensitizes both parental and Ptx-resistant TNBC cells to Ptx. These results indicate that LIS1/PAFAH1B1 may be a novel target for the development of new anti-mitotic agents for treating TNBC, particularly in the context of paclitaxel resistance.","PeriodicalId":15140,"journal":{"name":"Journal of Biological Chemistry","volume":"30 1","pages":"110235"},"PeriodicalIF":4.8,"publicationDate":"2025-05-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144083308","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0