Cell reports最新文献_第10页

Base-excision repair pathway regulates transcription-replication conflicts in pancreatic ductal adenocarcinoma. 碱基切除修复途径调节胰腺导管腺癌的转录-复制冲突

IF 7.5 1区生物学

Cell reports Pub Date : 2024-10-22 Epub Date: 2024-10-04 DOI: 10.1016/j.celrep.2024.114820

Fan Meng, Tiane Li, Anup K Singh, Yingying Wang, Marc Attiyeh, Fatemeh Kohram, Qianhua Feng, Yun R Li, Binghui Shen, Terence Williams, Yilun Liu, Mustafa Raoof

{"title":"Base-excision repair pathway regulates transcription-replication conflicts in pancreatic ductal adenocarcinoma.","authors":"Fan Meng, Tiane Li, Anup K Singh, Yingying Wang, Marc Attiyeh, Fatemeh Kohram, Qianhua Feng, Yun R Li, Binghui Shen, Terence Williams, Yilun Liu, Mustafa Raoof","doi":"10.1016/j.celrep.2024.114820","DOIUrl":"10.1016/j.celrep.2024.114820","url":null,"abstract":"Oncogenic mutations (such as in KRAS) can dysregulate transcription and replication, leading to transcription-replication conflicts (TRCs). Here, we demonstrate that TRCs are enriched in human pancreatic ductal adenocarcinoma (PDAC) compared to other common solid tumors or normal cells. Several orthogonal approaches demonstrated that TRCs are oncogene dependent. A small interfering RNA (siRNA) screen identified several factors in the base-excision repair (BER) pathway as main regulators of TRCs in PDAC cells. Inhibitors of BER pathway (methoxyamine and CRT) enhanced TRCs. Mechanistically, BER pathway inhibition severely altered RNA polymerase II (RNAPII) and R-loop dynamics at nascent DNA, causing RNAPII trapping and contributing to enhanced TRCs. The ensuing DNA damage activated the ATR-Chk1 pathway. Co-treatment with ATR inhibitor (VX970) and BER inhibitor (methoxyamine) at clinically relevant doses synergistically enhanced DNA damage and reduced cell proliferation in PDAC cells. The study provides mechanistic insights into the regulation of TRCs in PDAC by the BER pathway, which has biologic and therapeutic implications.","PeriodicalId":9798,"journal":{"name":"Cell reports","volume":"43 10","pages":"114820"},"PeriodicalIF":7.5,"publicationDate":"2024-10-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142379145","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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

High-content phenotypic analysis of a C. elegans recombinant inbred population identifies genetic and molecular regulators of lifespan. 对 elegans 近交系重组种群的高含量表型分析确定了寿命的遗传和分子调控因子。

IF 7.5 1区生物学

Cell reports Pub Date : 2024-10-22 Epub Date: 2024-10-04 DOI: 10.1016/j.celrep.2024.114836

Arwen W Gao, Gaby El Alam, Yunyun Zhu, Weisha Li, Jonathan Sulc, Xiaoxu Li, Elena Katsyuba, Terytty Y Li, Katherine A Overmyer, Amelia Lalou, Laurent Mouchiroud, Maroun Bou Sleiman, Matteo Cornaglia, Jean-David Morel, Riekelt H Houtkooper, Joshua J Coon, Johan Auwerx

{"title":"High-content phenotypic analysis of a C. elegans recombinant inbred population identifies genetic and molecular regulators of lifespan.","authors":"Arwen W Gao, Gaby El Alam, Yunyun Zhu, Weisha Li, Jonathan Sulc, Xiaoxu Li, Elena Katsyuba, Terytty Y Li, Katherine A Overmyer, Amelia Lalou, Laurent Mouchiroud, Maroun Bou Sleiman, Matteo Cornaglia, Jean-David Morel, Riekelt H Houtkooper, Joshua J Coon, Johan Auwerx","doi":"10.1016/j.celrep.2024.114836","DOIUrl":"10.1016/j.celrep.2024.114836","url":null,"abstract":"Lifespan is influenced by complex interactions between genetic and environmental factors. Studying those factors in model organisms of a single genetic background limits their translational value for humans. Here, we mapped lifespan determinants in 85 C. elegans recombinant inbred advanced intercross lines (RIAILs). We assessed molecular profiles-transcriptome, proteome, and lipidome-and life-history traits, including lifespan, development, growth dynamics, and reproduction. RIAILs exhibited large variations in lifespan, which correlated positively with developmental time. We validated three longevity modulators, including rict-1, gfm-1, and mltn-1, among the top candidates obtained from multiomics data integration and quantitative trait locus (QTL) mapping. We translated their relevance to humans using UK Biobank data and showed that variants in GFM1 are associated with an elevated risk of age-related heart failure. We organized our dataset as a resource that allows interactive explorations for new longevity targets.","PeriodicalId":9798,"journal":{"name":"Cell reports","volume":"43 10","pages":"114836"},"PeriodicalIF":7.5,"publicationDate":"2024-10-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142379147","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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

Hormone-mediated disassembly and inactivation of a plant E3 ubiquitin ligase complex. 激素介导的植物 E3 泛素连接酶复合物的解体和失活。

IF 7.5 1区生物学

Cell reports Pub Date : 2024-10-22 Epub Date: 2024-10-02 DOI: 10.1016/j.celrep.2024.114802

Cristina Martínez, Elisa Iniesto, Marta García-León, Daniel García-Corredera, Sandra Fonseca, César Santiago, Mei Yang, Renbo Yu, Haodong Chen, Eva Altmann, Martin Renatus, Xing Wang Deng, Vicente Rubio

{"title":"Hormone-mediated disassembly and inactivation of a plant E3 ubiquitin ligase complex.","authors":"Cristina Martínez, Elisa Iniesto, Marta García-León, Daniel García-Corredera, Sandra Fonseca, César Santiago, Mei Yang, Renbo Yu, Haodong Chen, Eva Altmann, Martin Renatus, Xing Wang Deng, Vicente Rubio","doi":"10.1016/j.celrep.2024.114802","DOIUrl":"10.1016/j.celrep.2024.114802","url":null,"abstract":"Phytohormone abscisic acid (ABA) regulates key plant development and environmental stress responses. The ubiquitin-proteasome system tightly controls ABA signaling. CULLIN4-RING (CRL4) E3 ubiquitin ligases use the substrate receptor module CONSTITUTIVELY PHOTOMORPHOGENIC1 (COP10)-DDB1-DET1-DDA1 (CDDD) to target Arabidopsis ABA receptor PYL8, acting as negative regulators of ABA responses. Conversely, ABA treatment attenuates PYL8 receptor degradation, although the molecular mechanism remained elusive. Here, we show that ABA promotes the disruption of CRL4-CDDD complexes, leading to PYL8 stabilization. ABA-mediated CRL4-CDDD dissociation likely involves an altered association between DDA1-containing complexes and the COP9 signalosome (CSN), a master regulator of the assembly of cullin-based E3 ligases, including CRL4-CDDD. Indeed, treatment with CSN inhibitor CSN5i-3 suppresses the ABA effect on CRL4-CDDD assembly. Our findings indicate that ABA stabilizes PYL8 by altering the dynamics of the CRL4-CDDD-CSN complex association, showing a regulatory mechanism by which a plant hormone inhibits an E3 ubiquitin ligase to protect its own receptors from degradation.","PeriodicalId":9798,"journal":{"name":"Cell reports","volume":"43 10","pages":"114802"},"PeriodicalIF":7.5,"publicationDate":"2024-10-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142375204","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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

Genomic convergence in terrestrial root plants through tandem duplication in response to soil microbial pressures. 陆生根系植物在土壤微生物压力下通过串联复制实现基因组趋同。

IF 7.5 1区生物学

Cell reports Pub Date : 2024-10-22 Epub Date: 2024-09-26 DOI: 10.1016/j.celrep.2024.114786

Wenwu Wu, Liangyu Guo, Liufan Yin, Bijun Cai, Jing Li, Xiaoxiao Li, Jian Yang, Haichao Zhou, Zeng Tao, Yan Li

{"title":"Genomic convergence in terrestrial root plants through tandem duplication in response to soil microbial pressures.","authors":"Wenwu Wu, Liangyu Guo, Liufan Yin, Bijun Cai, Jing Li, Xiaoxiao Li, Jian Yang, Haichao Zhou, Zeng Tao, Yan Li","doi":"10.1016/j.celrep.2024.114786","DOIUrl":"10.1016/j.celrep.2024.114786","url":null,"abstract":"Despite increasing reports of convergent adaptation, evidence for genomic convergence across diverse species worldwide is lacking. Here, our study of 205 Archaeplastida genomes reveals evidence of genomic convergence through tandem duplication (TD) across different lineages of root plants despite their genomic diversity. TD-derived genes, notably prevalent in trees with developed root systems embedded in soil, are enriched in enzymatic catalysis and biotic stress responses, suggesting adaptations to environmental pressures. Correlation analyses suggest that many factors, particularly those related to soil microbial pressures, are significantly associated with TD dynamics. Conversely, flora transitioned to aquatic, parasitic, halophytic, or carnivorous lifestyles-reducing their interaction with soil microbes-exhibit a consistent decline in TD frequency. This trend is further corroborated in mangroves that independently adapted to hypersaline intertidal soils, characterized by diminished microbial activity. Our findings propose TD-driven genomic convergence as a widespread adaptation to soil microbial pressures among terrestrial root plants.","PeriodicalId":9798,"journal":{"name":"Cell reports","volume":"43 10","pages":"114786"},"PeriodicalIF":7.5,"publicationDate":"2024-10-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142342476","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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

Macrophage NRF1 promotes mitochondrial protein turnover via the ubiquitin proteasome system to limit mitochondrial stress and inflammation. 巨噬细胞 NRF1 通过泛素蛋白酶体系统促进线粒体蛋白质周转，从而限制线粒体压力和炎症。

IF 7.5 1区生物学

Cell reports Pub Date : 2024-10-22 Epub Date: 2024-09-25 DOI: 10.1016/j.celrep.2024.114780

Jiawei Yan, Xin Zhang, Huiying Wang, Xinglong Jia, Ruohong Wang, Shuangyang Wu, Zheng-Jiang Zhu, Minjia Tan, Tiffany Horng

{"title":"Macrophage NRF1 promotes mitochondrial protein turnover via the ubiquitin proteasome system to limit mitochondrial stress and inflammation.","authors":"Jiawei Yan, Xin Zhang, Huiying Wang, Xinglong Jia, Ruohong Wang, Shuangyang Wu, Zheng-Jiang Zhu, Minjia Tan, Tiffany Horng","doi":"10.1016/j.celrep.2024.114780","DOIUrl":"10.1016/j.celrep.2024.114780","url":null,"abstract":"Macrophage elaboration of inflammatory responses is dynamically regulated, shifting from acute induction to delayed suppression during the course of infection. Here, we show that such regulation of inflammation is modulated by dynamic shifts in metabolism. In macrophages exposed to the bacterial product lipopolysaccharide (LPS), an initial induction of protein biosynthesis is followed by compensatory induction of the transcription factor nuclear factor erythroid 2-like 1 (NRF1), leading to increased flux through the ubiquitin proteasome system (UPS). A major target of NRF1-mediated UPS flux is the mitochondrial proteome, and in the absence of NRF1, ubiquitinated mitochondrial proteins accumulate to trigger severe mitochondrial stress. Such mitochondrial stress engages the integrated stress response-ATF4 axis, which limits mitochondrial translation to attenuate mitochondrial stress but amplifies inflammatory responses to augment susceptibility to septic shock. Therefore, NRF1 mediates a dynamic regulation of mitochondrial proteostasis in inflammatory macrophages that contributes to curbing inflammatory responses.","PeriodicalId":9798,"journal":{"name":"Cell reports","volume":"43 10","pages":"114780"},"PeriodicalIF":7.5,"publicationDate":"2024-10-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142342480","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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

Phosphoproteomic subtyping of gastric cancer reveals dynamic transformation with chemotherapy and guides targeted cancer treatment. 胃癌磷蛋白体亚型分析揭示了化疗的动态转变，并为癌症靶向治疗提供指导。

IF 7.5 1区生物学

Cell reports Pub Date : 2024-10-22 Epub Date: 2024-10-01 DOI: 10.1016/j.celrep.2024.114774

Hirokazu Shoji, Hidekazu Hirano, Yosui Nojima, Daigo Gunji, Akina Shinkura, Satoshi Muraoka, Yuichi Abe, Ryohei Narumi, Chioko Nagao, Masahiko Aoki, Kazutaka Obama, Kazufumi Honda, Kenji Mizuguchi, Takeshi Tomonaga, Yutaka Saito, Takaki Yoshikawa, Ken Kato, Narikazu Boku, Jun Adachi

{"title":"Phosphoproteomic subtyping of gastric cancer reveals dynamic transformation with chemotherapy and guides targeted cancer treatment.","authors":"Hirokazu Shoji, Hidekazu Hirano, Yosui Nojima, Daigo Gunji, Akina Shinkura, Satoshi Muraoka, Yuichi Abe, Ryohei Narumi, Chioko Nagao, Masahiko Aoki, Kazutaka Obama, Kazufumi Honda, Kenji Mizuguchi, Takeshi Tomonaga, Yutaka Saito, Takaki Yoshikawa, Ken Kato, Narikazu Boku, Jun Adachi","doi":"10.1016/j.celrep.2024.114774","DOIUrl":"10.1016/j.celrep.2024.114774","url":null,"abstract":"There are only a few effective molecular targeted agents for advanced unresectable or recurrent advanced gastric cancer (AGC), which has a poor prognosis with a median survival time of less than 14 months. Focusing on phosphorylation signaling in cancer cells, we have been developing deep phosphoproteome analysis from minute endoscopic biopsy specimens frozen within 20 s of collection. Phosphoproteomic analysis of 127 fresh-frozen endoscopic biopsy samples from untreated patients with AGC revealed three subtypes reflecting different cellular signaling statuses. Subsequent serial biopsy analysis has revealed the dynamic mesenchymal transitions within cancer cells, along with the concomitant rewiring of the kinome network, ultimately resulting in the conversion to the epithelial-mesenchymal transition (EMT) subtype throughout treatment. We present our investigation of intracellular signaling related to the EMT in gastric cancer and propose therapeutic approaches targeting AXL. This study also provides a wealth of resources for the future development of treatments and biomarkers for AGC.","PeriodicalId":9798,"journal":{"name":"Cell reports","volume":" ","pages":"114774"},"PeriodicalIF":7.5,"publicationDate":"2024-10-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142364570","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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

CTNND2 moderates the pace of synaptic maturation and links human evolution to synaptic neoteny. CTNND2 可调节突触成熟的速度，并将人类进化与突触新生联系起来。

IF 7.5 1区生物学

Cell reports Pub Date : 2024-10-22 Epub Date: 2024-09-30 DOI: 10.1016/j.celrep.2024.114797

Nora Assendorp, Matteo Fossati, Baptiste Libé-Philippot, Eirini Christopoulou, Marine Depp, Roberta Rapone, Florent Dingli, Damarys Loew, Pierre Vanderhaeghen, Cécile Charrier

{"title":"CTNND2 moderates the pace of synaptic maturation and links human evolution to synaptic neoteny.","authors":"Nora Assendorp, Matteo Fossati, Baptiste Libé-Philippot, Eirini Christopoulou, Marine Depp, Roberta Rapone, Florent Dingli, Damarys Loew, Pierre Vanderhaeghen, Cécile Charrier","doi":"10.1016/j.celrep.2024.114797","DOIUrl":"10.1016/j.celrep.2024.114797","url":null,"abstract":"Human-specific genes are potential drivers of brain evolution. Among them, SRGAP2C has contributed to the emergence of features characterizing human cortical synapses, including their extended period of maturation. SRGAP2C inhibits its ancestral copy, the postsynaptic protein SRGAP2A, but the synaptic molecular pathways differentially regulated in humans by SRGAP2 proteins remain largely unknown. Here, we identify CTNND2, a protein implicated in severe intellectual disability (ID) in Cri-du-Chat syndrome, as a major partner of SRGAP2. We demonstrate that CTNND2 slows synaptic maturation and promotes neuronal integrity. During postnatal development, CTNND2 moderates neuronal excitation and excitability. In adults, it supports synapse maintenance. While CTNND2 deficiency is deleterious and results in synaptic loss of SYNGAP1, another major ID-associated protein, the human-specific protein SRGAP2C, enhances CTNND2 synaptic accumulation in human neurons. Our findings suggest that CTNND2 regulation by SRGAP2C contributes to synaptic neoteny in humans and link human-specific and ID genes at the synapse.","PeriodicalId":9798,"journal":{"name":"Cell reports","volume":"43 10","pages":"114797"},"PeriodicalIF":7.5,"publicationDate":"2024-10-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142364571","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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

SRF promotes long-range chromatin loop formation and stem cell pluripotency. SRF 促进长程染色质环的形成和干细胞的多能性。

IF 7.5 1区生物学

Cell reports Pub Date : 2024-10-22 Epub Date: 2024-10-10 DOI: 10.1016/j.celrep.2024.114846

Pavel Tsaytler, Gaby Blaess, Manuela Scholze-Wittler, David Meierhofer, Lars Wittler, Frederic Koch, Bernhard G Herrmann

引用次数: 0

Nuclear HMGB1 is critical for CD8 T cell IFN-γ production and anti-tumor immunity. 核 HMGB1 对 CD8 T 细胞 IFN-γ 的产生和抗肿瘤免疫至关重要。

IF 7.5 1区生物学

Cell reports Pub Date : 2024-10-22 Epub Date: 2024-10-10 DOI: 10.1016/j.celrep.2024.114886

Zhiguang Xu, Weiying Ma, Ji Wang, Haofan Chen, Hui Li, Zhinan Yin, Jianlei Hao, Kebing Chen

引用次数: 0

ILC2-derived CGRP triggers acute inflammation and nociceptive responses in bacterial cystitis. 源自 ILC2 的 CGRP 触发细菌性膀胱炎的急性炎症和痛觉反应。

IF 7.5 1区生物学

Cell reports Pub Date : 2024-10-22 Epub Date: 2024-10-16 DOI: 10.1016/j.celrep.2024.114859

Zizhuo Yang, Yaxiao Liu, Yinrui Xiang, Rui Chen, Lipeng Chen, Shuai Wang, Linchen Lv, Maolin Zang, Nan Zhou, Shiyang Li, Benkang Shi, Yan Li

{"title":"ILC2-derived CGRP triggers acute inflammation and nociceptive responses in bacterial cystitis.","authors":"Zizhuo Yang, Yaxiao Liu, Yinrui Xiang, Rui Chen, Lipeng Chen, Shuai Wang, Linchen Lv, Maolin Zang, Nan Zhou, Shiyang Li, Benkang Shi, Yan Li","doi":"10.1016/j.celrep.2024.114859","DOIUrl":"10.1016/j.celrep.2024.114859","url":null,"abstract":"Calcitonin gene-related peptide (CGRP), a neuropeptide involved in nociceptor neuronal function, plays a critical role in mediating neuroinflammation and pain. In this study, we find that bladder group 2 innate lymphoid cells (ILC2s) function as primary producers of CGRP in the early phase of bacterial cystitis, contributing to increased inflammation, altered voiding behavior, and heightened pelvic allodynia. Furthermore, we demonstrate that interleukin (IL)-33, a cytokine secreted by urothelial cells, upregulates CGRP production by ILC2s in the bladder during uropathogenic Escherichia coli (UPEC) infection. Moreover, our research reveals that monocytes expressing high levels of receptor activity-modifying protein 1 (RAMP1), a CGRP receptor, mediate the pro-inflammatory effects of CGRP-producing ILC2s. In summary, our results underscore the significance of the immune cell-derived neuropeptides in the pathology of UPEC infection, suggesting a promising therapeutic approach targeting the IL-33-ILC2-CGRP axis for managing lower urinary tract symptoms in bacterial cystitis.","PeriodicalId":9798,"journal":{"name":"Cell reports","volume":"43 10","pages":"114859"},"PeriodicalIF":7.5,"publicationDate":"2024-10-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142459144","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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