FEBS Letters最新文献_第2页

Senescent cells acquire resistance to cystine deprivation-induced ferroptosis via the PPARα-PDK4-phosphorylated PDH axis. 衰老细胞通过ppar α- pdk4磷酸化的PDH轴获得对胱氨酸剥夺诱导的铁下垂的抗性。

IF 3 4区生物学

FEBS Letters Pub Date : 2026-04-19 DOI: 10.1002/1873-3468.70332

Shiho Machii, Kazushi Morimoto, Pakawit Lerksaipheng, Mirinthorn Jutanom, Ken-Ichi Yamada

引用次数: 0

An isoform of 14-3-3 protein regulates transbilayer lipid movement at the plasma membrane. 14-3-3蛋白的异构体调节质膜上的跨双分子层脂质运动。

IF 3 4区生物学

FEBS Letters Pub Date : 2026-04-15 DOI: 10.1002/1873-3468.70338

Akiko Yamaji-Hasegawa, Akira Hattori, Masafumi Tsujimoto, Toshihide Kobayashi

{"title":"An isoform of 14-3-3 protein regulates transbilayer lipid movement at the plasma membrane.","authors":"Akiko Yamaji-Hasegawa, Akira Hattori, Masafumi Tsujimoto, Toshihide Kobayashi","doi":"10.1002/1873-3468.70338","DOIUrl":"https://doi.org/10.1002/1873-3468.70338","url":null,"abstract":"Exogenous phosphatidylserine (PS) is cytotoxic to Chinese hamster ovary (CHO) cells with a PS-resistant CHO cell mutant exhibiting impaired transbilayer movement of a fluorescent PS analog at the plasma membrane. Here, we demonstrate that both mRNA and protein levels of 14-3-3 zeta are markedly reduced in this mutant, while knockdown of 14-3-3 zeta in wild-type CHO cells confers partial resistance to exogenous PS. Consistently, these knockdown cells display defective transbilayer movement of 1-palmitoyl-2-{6-[(7-nitro-1,3-benz-2-oxadiazol-4-yl) amino] hexanoyl}-sn-glycero-3-phosphoserine (C6-NBD-PS). However, 14-3-3 zeta knockdown does not further enhance PS resistance in ATP11C-deficient cells. These findings indicate that 14-3-3 zeta plays a regulatory role in ATP11C-dependent transbilayer movement of PS at the plasma membrane. Impact statement 14-3-3ζ regulates ATP11C-dependent phosphatidylserine (PS) transbilayer movement at the plasma membrane. Reduced 14-3-3ζ impairs PS flipping and confers resistance to exogenous PS in CHO cells, identifying 14-3-3ζ as a key modulator of phospholipid asymmetry and lipid-induced cytotoxicity.","PeriodicalId":12142,"journal":{"name":"FEBS Letters","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2026-04-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147689035","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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

Genetically encoded lockdown of SERCA in the endoplasmic reticulum membrane arrests Ca²⁺ signaling through proximity-covalent crosslinking. 内质网膜中SERCA的基因编码锁定通过近共价交联阻止Ca2+信号传导。

IF 3 4区生物学

FEBS Letters Pub Date : 2026-04-15 DOI: 10.1002/1873-3468.70342

Yiying Li, Kozo Hamada

{"title":"Genetically encoded lockdown of SERCA in the endoplasmic reticulum membrane arrests Ca2+ signaling through proximity-covalent crosslinking.","authors":"Yiying Li, Kozo Hamada","doi":"10.1002/1873-3468.70342","DOIUrl":"10.1002/1873-3468.70342","url":null,"abstract":"Reversible conformational dynamics of membrane proteins are essential for intracellular signaling, but no method enables their irreversible arrest in living cells. Here, we developed a genetically encoded proximity-based lockdown enzyme derived from an engineered transglutaminase catalytic core (TGC) that covalently crosslinks membrane proteins. By fusing TGC to the endoplasmic reticulum (ER)-resident microprotein ALN encoded by a short open reading frame (sORF), we created an organelle-specific module that selectively catalyzes covalent crosslinking within the SERCA Ca2+ pump, strongly suppressing its ATP-dependent pump activity and arresting ER Ca2+ signaling. This engineered lockdown enzyme remodels ER membrane protein architecture and restricts conformational dynamics, providing a versatile platform for long-term covalent control of intracellular signaling and a foundation for future therapeutic cellular applications. Impact statement Our proximity-based lockdown enzyme, engineered from microbial transglutaminase, provides a new strategy to covalently arrest the conformational states of organelle-resident membrane proteins in living cells, enabling long-term control of intracellular signaling and establishing a foundation for next-generation cellular therapeutics.","PeriodicalId":12142,"journal":{"name":"FEBS Letters","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2026-04-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147689033","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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

NONO promotes MYB expression and splicing by interacting with enhancer lncRNA MY34UE-AS in human leukemia cells NONO在人白血病细胞中通过与增强子lncRNA MY34UE-AS相互作用促进MYB的表达和剪接。

IF 3 4区生物学

FEBS Letters Pub Date : 2026-04-13 Epub Date: 2026-03-10 DOI: 10.1002/1873-3468.70316

Siyu Shen, Yucheng Wang, Xiaoxiao Tao, Zhenhua Zhou, Songya Qu, Junfang Zhang, Bingshe Han

引用次数: 0

Crosstalk between the ribosome quality control-associated E3 ubiquitin ligases LTN1 and RNF10 核糖体质量控制相关E3泛素连接酶LTN1和RNF10之间的串扰。

IF 3 4区生物学

FEBS Letters Pub Date : 2026-04-13 Epub Date: 2025-12-26 DOI: 10.1002/1873-3468.70230

Yuxi Huang, Satoshi Hashimoto, Sota Ito, Chisato Kikuguchi, Miho Hoshi, Kiyoshi Yamaguchi, Yoichi Furukawa, Toru Suzuki, Toshifumi Inada

引用次数: 0

PICALM::MLLT10 translocated leukemia MLLT10易位性白血病。

IF 3 4区生物学

FEBS Letters Pub Date : 2026-04-13 Epub Date: 2026-01-14 DOI: 10.1002/1873-3468.70279

John M. Cullen, Antonia C. Nakatsugawa, Natalie Barton, Henry Haines, Gary S. Stein, Janet L. Stein, Daniel S. Wechsler, Jessica L. Heath

{"title":"PICALM::MLLT10 translocated leukemia","authors":"John M. Cullen, Antonia C. Nakatsugawa, Natalie Barton, Henry Haines, Gary S. Stein, Janet L. Stein, Daniel S. Wechsler, Jessica L. Heath","doi":"10.1002/1873-3468.70279","DOIUrl":"10.1002/1873-3468.70279","url":null,"abstract":"The t(10;11)(p13;q14-21) PICALM::MLLT10 chromosomal translocation results in the production of the CALM-AF10 fusion oncoprotein and is a driver mutation in both acute myeloid and T-lymphoblastic leukemia. PICALM::MLLT10 translocated leukemia is primarily an epigenetically driven disease. Global hypomethylation results in genomic instability, while focal H3K79 hypermethylation at target genes induces cell proliferation and blocks differentiation. Nucleocytoplasmic shuttling of CALM-AF10 and its protein partners and impaired endocytosis at the plasma membrane further influence the leukemic phenotype. Leukemias characterized by PICALM::MLLT10 have historically been recognized to portend a poor prognosis; however, insights from larger patient cohorts provide refinement to the prognostic relevance of this chromosomal translocation, highlighting chemotherapy resistance in this leukemic subtype. In addition, a deeper biological understanding of the disease hints at potential therapeutic targets. This approach is demonstrated in the recent promising results achieved utilizing venetoclax, a BCL2 inhibitor, in patients with PICALM::MLLT10 acute leukemia. Herein, we provide updates on the pathophysiology, clinical presentation, prognosis, and treatment of PICALM::MLLT10 acute leukemia.","PeriodicalId":12142,"journal":{"name":"FEBS Letters","volume":"600 7","pages":"1028-1042"},"PeriodicalIF":3.0,"publicationDate":"2026-04-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://febs.onlinelibrary.wiley.com/doi/epdf/10.1002/1873-3468.70279","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145965738","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

GTPase Npa3-TORC1 crosstalk suggests genetic coordination of nutrient sensing and translational control GTPase Npa3-TORC1串扰提示营养感知和翻译控制的遗传协调。

IF 3 4区生物学

FEBS Letters Pub Date : 2026-04-13 Epub Date: 2026-01-16 DOI: 10.1002/1873-3468.70285

Martín Mora-García, Alda DelaGarza-Varela, Yolanda Rebolloso-Gómez, Tania Félix-Pérez, Sonia G. Peña-Gómez, Lina Riego-Ruiz, Roberto Sánchez-Olea, Mónica R. Calera

{"title":"GTPase Npa3-TORC1 crosstalk suggests genetic coordination of nutrient sensing and translational control","authors":"Martín Mora-García, Alda DelaGarza-Varela, Yolanda Rebolloso-Gómez, Tania Félix-Pérez, Sonia G. Peña-Gómez, Lina Riego-Ruiz, Roberto Sánchez-Olea, Mónica R. Calera","doi":"10.1002/1873-3468.70285","DOIUrl":"10.1002/1873-3468.70285","url":null,"abstract":"The GPN-loop GTPase Npa3 plays a critical role in RNA polymerase II (RNAPII) assembly and nuclear import. We employed here the npa3ΔC mutant, which supports normal RNAPII localization and function, to investigate potential links between Npa3 and target of rapamycin complex I (TORC1) signaling. The npa3ΔC cells exhibited increased sensitivity to rapamycin, a synthetic sickness interaction with tor1Δ, and a delayed growth recovery rate from rapamycin-induced G1 arrest. Co-expression analysis identified LTV1, a gene involved in TORC1 signaling and ribosome nuclear export, as one of the top genes co-expressed with NPA3. Furthermore, overexpression of eukaryotic translation initiation factor 1A (eIF1A, TIF11) or regulator of heterotrimeric G-protein signaling (RGS2) restored growth in npa3ΔC cells under rapamycin treatment. Interestingly, RGS2 also rescued growth under hygromycin B stress. Our findings suggest a genetic interplay between Npa3 and TORC1.","PeriodicalId":12142,"journal":{"name":"FEBS Letters","volume":"600 7","pages":"1088-1100"},"PeriodicalIF":3.0,"publicationDate":"2026-04-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145989007","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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 E3 ubiquitin ligase UBR5 promotes ubiquitylation and degradation of the chromatin regulator ATAD2. E3泛素连接酶UBR5促进泛素化和染色质调节因子ATAD2的降解。

IF 3 4区生物学

FEBS Letters Pub Date : 2026-04-13 DOI: 10.1002/1873-3468.70339

Rikuto Honda, Miyu Takao, Yoshino Akizuki, Fumiaki Ohtake

引用次数: 0

Inhibiting stearoyl-CoA desaturase suppresses bone metastatic prostate cancer by modulating cellular stress, mTOR signaling, and DNA damage response 抑制硬脂酰辅酶a去饱和酶通过调节细胞应激、mTOR信号和DNA损伤反应来抑制骨转移性前列腺癌。

IF 3 4区生物学

FEBS Letters Pub Date : 2026-04-13 Epub Date: 2026-01-28 DOI: 10.1002/1873-3468.70290

Alexis Wilson, Mackenzie K Herroon, Shane Mecca, Laimar C Garmo, Jacob Lindquist, Shrila Rajendran, Steve M. Patrick, Izabela Podgorski

{"title":"Inhibiting stearoyl-CoA desaturase suppresses bone metastatic prostate cancer by modulating cellular stress, mTOR signaling, and DNA damage response","authors":"Alexis Wilson, Mackenzie K Herroon, Shane Mecca, Laimar C Garmo, Jacob Lindquist, Shrila Rajendran, Steve M. Patrick, Izabela Podgorski","doi":"10.1002/1873-3468.70290","DOIUrl":"10.1002/1873-3468.70290","url":null,"abstract":"The mechanisms supporting progression of metastatic prostate cancer (PCa) in adipocyte-rich bone marrow remain unclear. We hypothesized that stearoyl-coenzyme A desaturase (SCD) promotes PCa survival in bone by modulating stress responses and regulating lipid peroxidation. We show that SCD-high PCa cells are sensitive to SCD loss, showing smaller spheroids, reduced mTOR signaling, and elevated endoplasmic reticulum (ER) stress. SCD expression is further augmented by adipocytes, and SCD loss induces DNA damage and repair activation only with adipocyte exposure. In vivo, pharmacological SCD inhibition reduces tumor size and increases ER stress and DNA damage in SCD-high-expressing bone tumors. These findings suggest SCD plays a role in redox regulation and DNA repair sensitivity, with therapeutic potential for targeting DNA repair pathways in combination with SCD inhibition.\u0000 \u0000 ","PeriodicalId":12142,"journal":{"name":"FEBS Letters","volume":"600 7","pages":"1043-1061"},"PeriodicalIF":3.0,"publicationDate":"2026-04-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12967245/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146104474","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Genetic interactions, synthetic lethality and complexity in cancer vulnerability mapping—Insights and perspectives from the 2nd EuroDepMap symposium 基因相互作用、合成致死率和癌症易感性定位的复杂性——来自第二届EuroDepMap研讨会的见解和观点。

IF 3 4区生物学

FEBS Letters Pub Date : 2026-04-13 Epub Date: 2026-02-22 DOI: 10.1002/1873-3468.70306

Ludovica Proietti, Pedro Beltrao, Alejandra Bruna, Isidro Cortés-Ciriano, Mathew J. Garnett, Emanuel Gonçalves, Carmen Herranz-Ors, Manuel Kaulich, Christopher J. Lord, Evangelia Petsalaki, Roland Rad, Colm J. Ryan, Aurora Savino, Debora Sesia, Lodewyk Wessels, Francesco Iorio

{"title":"Genetic interactions, synthetic lethality and complexity in cancer vulnerability mapping—Insights and perspectives from the 2nd EuroDepMap symposium","authors":"Ludovica Proietti, Pedro Beltrao, Alejandra Bruna, Isidro Cortés-Ciriano, Mathew J. Garnett, Emanuel Gonçalves, Carmen Herranz-Ors, Manuel Kaulich, Christopher J. Lord, Evangelia Petsalaki, Roland Rad, Colm J. Ryan, Aurora Savino, Debora Sesia, Lodewyk Wessels, Francesco Iorio","doi":"10.1002/1873-3468.70306","DOIUrl":"10.1002/1873-3468.70306","url":null,"abstract":"Large-scale perturbational approaches have transformed cancer research, enabling systematic identification of tumour-specific dependencies and therapeutic vulnerabilities. However, many clinically relevant vulnerabilities arise from genetic interactions, including synthetic lethal and buffering relationships, and are shaped by cellular state, lineage and treatment history. Interpreting complex dependency landscapes increasingly relies on advanced computational and AI-based approaches integrating molecular, phenotypic and contextual information. In this rapidly evolving setting, dedicated forums are needed to connect experimental and computational perspectives. Following the success of the inaugural European Cancer Dependency Map Symposium, the 2nd EuroDepMap was held on 20 November 2025 at Human Technopole in Milan, bringing together leading scientists in functional genomics, genome-editing screens, disease models and AI-driven analysis, marking a pivotal moment for the field.","PeriodicalId":12142,"journal":{"name":"FEBS Letters","volume":"600 7","pages":"997-1005"},"PeriodicalIF":3.0,"publicationDate":"2026-04-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://febs.onlinelibrary.wiley.com/doi/epdf/10.1002/1873-3468.70306","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147270259","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0