Molecular Cell最新文献_第9页

The role of protein lactylation: A kaleidoscopic post-translational modification in cancer 蛋白质乳酸化的作用：癌症中万花筒般的翻译后修饰

IF 16 1区生物学

Molecular Cell Pub Date : 2025-03-11 DOI: 10.1016/j.molcel.2025.02.011

Marta Iozzo, Elisa Pardella, Elisa Giannoni, Paola Chiarugi

{"title":"The role of protein lactylation: A kaleidoscopic post-translational modification in cancer","authors":"Marta Iozzo, Elisa Pardella, Elisa Giannoni, Paola Chiarugi","doi":"10.1016/j.molcel.2025.02.011","DOIUrl":"https://doi.org/10.1016/j.molcel.2025.02.011","url":null,"abstract":"The recently discovered lysine lactylation represents a critical post-translational modification with widespread implications in epigenetics and cancer biology. Initially identified on histones, lysine lactylation has been also described on non-histone proteins, playing a pivotal role in transcriptional activation, protein function, and cellular processes. Two major sources of the lactyl moiety have been currently distinguished: L-lactyl-CoA (precursor of the L-lactyl moiety) and S-D-lactylglutathione (precursor of the D-lactyl moiety), which enable enzymatic and non-enzymatic mechanisms of lysine lactylation, respectively. Although the specific writers, erasers, and readers of this modification are still unclear, acetyltransferases and deacetylases have been proposed as crucial mediators of lysine lactylation. Remarkably, lactylation exerts significant influence on critical cancer-related pathways, thereby shaping cellular behavior during malignant transformation and the metastatic cascade. Hence, as recent insights into lysine lactylation underscore its growing potential in tumor biology, targeting this modification is emerging as a significant opportunity for cancer treatment.","PeriodicalId":18950,"journal":{"name":"Molecular Cell","volume":"20 1","pages":""},"PeriodicalIF":16.0,"publicationDate":"2025-03-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143590054","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

Exportin-1 functions as an adaptor for transcription factor-mediated docking of chromatin at the nuclear pore complex export -1作为转录因子介导的核孔复合物染色质对接的接头

IF 16 1区生物学

Molecular Cell Pub Date : 2025-03-10 DOI: 10.1016/j.molcel.2025.02.013

Tiffany Ge, Donna Garvey Brickner, Kara Zehr, D. Jake VanBelzen, Wenzhu Zhang, Christopher Caffalette, Gavin C. Moeller, Sara Ungerleider, Nikita Marcou, Alexis Jacob, Vu Q. Nguyen, Brian Chait, Michael P. Rout, Jason H. Brickner

{"title":"Exportin-1 functions as an adaptor for transcription factor-mediated docking of chromatin at the nuclear pore complex","authors":"Tiffany Ge, Donna Garvey Brickner, Kara Zehr, D. Jake VanBelzen, Wenzhu Zhang, Christopher Caffalette, Gavin C. Moeller, Sara Ungerleider, Nikita Marcou, Alexis Jacob, Vu Q. Nguyen, Brian Chait, Michael P. Rout, Jason H. Brickner","doi":"10.1016/j.molcel.2025.02.013","DOIUrl":"https://doi.org/10.1016/j.molcel.2025.02.013","url":null,"abstract":"Nuclear pore proteins (nucleoporins [Nups]) physically interact with hundreds of chromosomal sites, impacting transcription. In yeast, transcription factors mediate interactions between Nups and enhancers and promoters. To define the molecular basis of this mechanism, we exploited a separation-of-function mutation in the Gcn4 transcription factor that blocks its interaction with the nuclear pore complex (NPC). This mutation reduces the interaction of Gcn4 with the highly conserved nuclear export factor Crm1/Xpo1. Crm1 and Nups co-occupy enhancers, and Crm1 inhibition blocks interaction of the nuclear pore protein Nup2 with the genome. In vivo, Crm1 interacts stably with the NPC and in vitro, Crm1 binds directly to both Gcn4 and Nup2. Importantly, the interaction between Crm1 and Gcn4 requires neither Ran-guanosine triphosphate (GTP) nor the nuclear export sequence binding site. Finally, Crm1 and Ran-GTP stimulate DNA binding by Gcn4, suggesting that allosteric coupling between Crm1-Ran-GTP binding and DNA binding facilitates the docking of transcription-factor-bound enhancers at the NPC.","PeriodicalId":18950,"journal":{"name":"Molecular Cell","volume":"18 1","pages":""},"PeriodicalIF":16.0,"publicationDate":"2025-03-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143582493","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

Pioneer and PRDM transcription factors coordinate bivalent epigenetic states to safeguard cell fate 先锋和PRDM转录因子协调二价表观遗传状态，以保护细胞命运

IF 16 1区生物学

Molecular Cell Pub Date : 2025-03-07 DOI: 10.1016/j.molcel.2025.02.031

Satoshi Matsui, Marissa Granitto, Morgan Buckley, Katie Ludwig, Sandra Koigi, Joseph Shiley, William J. Zacharias, Christopher N. Mayhew, Hee-Woong Lim, Makiko Iwafuchi

引用次数: 0

Single-cell multi-omics tell the secrets of plant immunity 单细胞多组学揭示植物免疫的秘密

IF 16 1区生物学

Molecular Cell Pub Date : 2025-03-06 DOI: 10.1016/j.molcel.2025.02.008

Jian-Min Zhou, Wei Wang

引用次数: 0

Come together, right now! ZCCHC3 orchestrates cytosolic nucleic acid sensing through phase condensation 现在就一起来！ZCCHC3通过相凝聚协调胞质核酸传感

IF 16 1区生物学

Molecular Cell Pub Date : 2025-03-06 DOI: 10.1016/j.molcel.2025.02.009

Rebecca Barker, Eva Bartok

引用次数: 0

SUMO4 promotes SUMO deconjugation required for DNA double-strand-break repair SUMO4促进DNA双链断裂修复所需的SUMO解偶联

IF 16 1区生物学

Molecular Cell Pub Date : 2025-03-06 DOI: 10.1016/j.molcel.2025.02.004

Alexander J. Garvin, Alexander J. Lanz, George E. Ronson, Matthew J.W. Mackintosh, Katarzyna Starowicz, Alexandra K. Walker, Yara Aghabi, Hannah MacKay, Ruth M. Densham, Jai S. Bhachoo, Aneika C. Leney, Joanna R. Morris

引用次数: 0

Transcription-coupled AID deamination damage depends on ELOF1-associated RNA polymerase II 转录偶联的AID脱质损伤依赖于elof1相关的RNA聚合酶II

IF 16 1区生物学

Molecular Cell Pub Date : 2025-03-05 DOI: 10.1016/j.molcel.2025.02.006

Pengfei Dai, Yuanqing Tan, Yifeng Luo, Tingting Liu, Yanchao Huang, Yafang Shang, Min Emma Huang, Xiaojing Liu, Senxin Zhang, Yanyan Wang, Qian-Xi Li, Niu Li, Lulu Li, Yining Qin, Junqi Liu, Liu Daisy Liu, Xia Xie, Yanni Cai, Fei Xavier Chen, Xiaoqi Zheng, Fei-Long Meng

{"title":"Transcription-coupled AID deamination damage depends on ELOF1-associated RNA polymerase II","authors":"Pengfei Dai, Yuanqing Tan, Yifeng Luo, Tingting Liu, Yanchao Huang, Yafang Shang, Min Emma Huang, Xiaojing Liu, Senxin Zhang, Yanyan Wang, Qian-Xi Li, Niu Li, Lulu Li, Yining Qin, Junqi Liu, Liu Daisy Liu, Xia Xie, Yanni Cai, Fei Xavier Chen, Xiaoqi Zheng, Fei-Long Meng","doi":"10.1016/j.molcel.2025.02.006","DOIUrl":"https://doi.org/10.1016/j.molcel.2025.02.006","url":null,"abstract":"In adaptive immunity, transcription-coupled damage (TCD) is introduced into antibody genes by activation-induced cytidine deaminase (AID) to diversify antibody repertoire. However, the coordination between transcription and DNA damage/repair remains elusive. Here, we find that transcription elongation factor 1 (ELOF1) stabilizes paused RNA polymerase II (RNAPII) at transcription barriers, providing a platform for transcription-coupled DNA damage/repair. Using a genetic screen, we discover that ELOF1 is required for AID targeting and that ELOF1 deficiency results in defective antibody class switch recombination and somatic hypermutation in mice. While downstream transcription-coupled repair factors are dispensable for AID damage, ELOF1 mechanistically facilitates both TCD and repair by stabilizing chromatin-bound RNAPII. In ELOF1-deficient cells, paused RNAPII tends to detach from chromatin and fails to recruit factors to induce or repair DNA damage. Our study places ELOF1 at the center of transcription-coupled DNA metabolism processes and suggests a transition of RNAPII from elongation to a DNA damage/repair scaffold.","PeriodicalId":18950,"journal":{"name":"Molecular Cell","volume":"42 1","pages":""},"PeriodicalIF":16.0,"publicationDate":"2025-03-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143546600","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

Transcription elongation factor ELOF1 is required for efficient somatic hypermutation and class switch recombination 转录延伸因子ELOF1是高效体细胞超突变和类开关重组所必需的

IF 16 1区生物学

Molecular Cell Pub Date : 2025-03-05 DOI: 10.1016/j.molcel.2025.02.007

Lizhen Wu, Anurupa Devi Yadavalli, Filip Senigl, Gabriel Matos-Rodrigues, Dijin Xu, Andreas P. Pintado-Urbanc, Matthew D. Simon, Wei Wu, André Nussenzweig, David G. Schatz

{"title":"Transcription elongation factor ELOF1 is required for efficient somatic hypermutation and class switch recombination","authors":"Lizhen Wu, Anurupa Devi Yadavalli, Filip Senigl, Gabriel Matos-Rodrigues, Dijin Xu, Andreas P. Pintado-Urbanc, Matthew D. Simon, Wei Wu, André Nussenzweig, David G. Schatz","doi":"10.1016/j.molcel.2025.02.007","DOIUrl":"https://doi.org/10.1016/j.molcel.2025.02.007","url":null,"abstract":"Somatic hypermutation (SHM) and class switch recombination (CSR) diversify immunoglobulin (Ig) genes and are initiated by the activation-induced deaminase (AID), a single-stranded DNA cytidine deaminase thought to engage its substrate during RNA polymerase II (RNAPII) transcription. Through a genetic screen, we identified numerous potential factors involved in SHM, including elongation factor 1 homolog (ELOF1), a component of the RNAPII elongation complex that functions in transcription-coupled nucleotide excision repair (TC-NER) and transcription elongation. Loss of ELOF1 compromises SHM, CSR, and AID action in mammalian B cells and alters RNAPII transcription by reducing RNAPII pausing downstream of transcription start sites and levels of serine 5 but not serine 2 phosphorylated RNAPII throughout transcribed genes. ELOF1 must bind to RNAPII to be a proximity partner for AID and to function in SHM and CSR, and TC-NER is not required for SHM. We propose that ELOF1 helps create the appropriate stalled RNAPII substrate on which AID acts.","PeriodicalId":18950,"journal":{"name":"Molecular Cell","volume":"35 1","pages":""},"PeriodicalIF":16.0,"publicationDate":"2025-03-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143546598","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

Histone variant H2BE enhances chromatin accessibility in neurons to promote synaptic gene expression and long-term memory 组蛋白变体H2BE增强神经元染色质可及性，促进突触基因表达和长期记忆

IF 16 1区生物学

Molecular Cell Pub Date : 2025-03-05 DOI: 10.1016/j.molcel.2025.02.028

Emily R. Feierman, Sean Louzon, Nicholas A. Prescott, Tracy Biaco, Qingzeng Gao, Qi Qiu, Kyuhyun Choi, Katherine C. Palozola, Anna J. Voss, Shreya D. Mehta, Camille N. Quaye, Katherine T. Lynch, Marc V. Fuccillo, Hao Wu, Yael David, Erica Korb

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A family of bacterial Josephin-like deubiquitinases with an irreversible cleavage mode 具有不可逆裂解模式的细菌约瑟芬样去泛素化酶家族

IF 16 1区生物学

Molecular Cell Pub Date : 2025-03-03 DOI: 10.1016/j.molcel.2025.02.002

Thomas Hermanns, Susanne Kolek, Matthias Uthoff, Richard A. de Heiden, Monique P.C. Mulder, Ulrich Baumann, Kay Hofmann

引用次数: 0