FEBS Open Bio最新文献_第3页

Hydrostatic pressure activates HIF-1α via β-catenin to promote stemness in breast cancer cells 静水压力通过β-连环蛋白激活HIF-1α促进乳腺癌细胞的干性。

IF 2.7 4区生物学

FEBS Open Bio Pub Date : 2026-10-01 Epub Date: 2026-06-01 DOI: 10.1002/2211-5463.70267

Da Zhai, Yong Xu, Jingjing Ma, Ratchanee Duangrat, Chen Yan, Jingyan Liang, Hua Wei, Bin Jiang, Tao-Sheng Li

{"title":"Hydrostatic pressure activates HIF-1α via β-catenin to promote stemness in breast cancer cells","authors":"Da Zhai, Yong Xu, Jingjing Ma, Ratchanee Duangrat, Chen Yan, Jingyan Liang, Hua Wei, Bin Jiang, Tao-Sheng Li","doi":"10.1002/2211-5463.70267","DOIUrl":"10.1002/2211-5463.70267","url":null,"abstract":"Tumor microenvironment plays a pivotal role in regulating the biological properties of cancer cells. Interstitial fluid hydrostatic pressure (HP) generally increases in malignant solid tumors. While our recent work has demonstrated that elevated HP stabilizes HIF-1α expression in cancer cells, here we further investigate whether elevated HP promotes cancer cells to acquire stemness features. Our results showed that exposure to 50 mmHg HP for 48 h did not significantly change the survival or morphology of human breast cancer cells. However, 50 mmHg HP stimulation significantly increased aldehyde dehydrogenase (ALDH) activity and upregulated HIF-1α and stemness markers (CD44 and SSEA-1) in MCF-7 and BT-474 but not in MDA-MB-453 breast cancer cell lines. Correspondingly, β-catenin was significantly enhanced in MCF-7 and BT-474 breast cancer cell lines under 50 mmHg HP stimulation and was negatively expressed in MDA-MB-453 breast cancer cells. Hypoxia (1% O2) exposure for 48 h also significantly enhanced the expression of β-catenin only in MCF-7 cells and BT-474 breast cancer cell lines, but increased HIF-1α expression and ALDH activity in all breast cancer cell lines tested, including the β-catenin-deficient MDA-MB-453 cells. Therefore, we conclude that elevated HP in malignant tumors may facilitate the acquisition of ‘stemness’ characteristics of cancer cells by enhancing HIF-1α expression via β-catenin.","PeriodicalId":12187,"journal":{"name":"FEBS Open Bio","volume":"16 10","pages":"1992-2002"},"PeriodicalIF":2.7,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13399563/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148143302","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

A light-triggered Time-Resolved X-ray Solution Scattering (TR-XSS) workflow with application to protein conformational dynamics 光触发时间分辨x射线溶液散射（TR-XSS）工作流程及其在蛋白质构象动力学中的应用。

IF 2.7 4区生物学

FEBS Open Bio Pub Date : 2026-10-01 Epub Date: 2026-02-11 DOI: 10.1002/2211-5463.70200

Fatemeh Sabzian-Molaei, Fredrik Orädd, Konstantinos Magkakis, Magnus Andersson

引用次数: 0

Time-restricted feeding prior to Mycobacterium tuberculosis infection reduces tissue CD4+ T cells with limited impact on bacterial clearance 结核分枝杆菌感染前的限时喂养减少了组织CD4+ T细胞，但对细菌清除的影响有限。

IF 2.7 4区生物学

FEBS Open Bio Pub Date : 2026-10-01 Epub Date: 2026-06-04 DOI: 10.1002/2211-5463.70263

Ashish Gupta, Nidhi Yadav, Subhasmita Das, R. Rajendra Kumar Reddy, Nupur Sharma, Amol Ratnakar Suryawanshi, Jaswinder Singh Maras, Ranjan Kumar Nanda

{"title":"Time-restricted feeding prior to Mycobacterium tuberculosis infection reduces tissue CD4+ T cells with limited impact on bacterial clearance","authors":"Ashish Gupta, Nidhi Yadav, Subhasmita Das, R. Rajendra Kumar Reddy, Nupur Sharma, Amol Ratnakar Suryawanshi, Jaswinder Singh Maras, Ranjan Kumar Nanda","doi":"10.1002/2211-5463.70263","DOIUrl":"10.1002/2211-5463.70263","url":null,"abstract":"The effects of time-restricted feeding (TRF) on immune responses during bacterial infection are not well-studied. Here, we subjected mice (6–8 weeks, male) to 8 h of TRF for 30 days and then infected them with a low dose of Mycobacterium tuberculosis (Mtb) H37Rv. During the first 15 days, TRF improved glucose tolerance with marginal weight loss. However, global serum and liver metabolomics alongside liver proteomics indicated that TRF perturbed fatty acid biosynthesis and degradation, steroid hormone biosynthesis, and tyrosine metabolism. Together, these results indicate that TRF potentially affected the distribution and functionality of host immune cells. TRF mice had similar mycobacterial burdens in lungs and spleen at 21 days postinfection but had significantly lower CD3+ T cells in bone marrow and CD4+ T cells in both bone marrow and lungs. Ultimately, we show that TRF induced changes in amino acid and lipid metabolism persist during Mtb infection.","PeriodicalId":12187,"journal":{"name":"FEBS Open Bio","volume":"16 10","pages":"1944-1957"},"PeriodicalIF":2.7,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13398685/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148155921","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

The crystal structure of the Borrelia burgdorferi nicotinamidase BBE22 resolves a long-standing annotation error 伯氏疏螺旋体烟酰胺酶BBE22的晶体结构解决了一个长期存在的注释错误。

IF 2.7 4区生物学

FEBS Open Bio Pub Date : 2026-10-01 Epub Date: 2026-05-11 DOI: 10.1002/2211-5463.70268

Kalvis Brangulis

{"title":"The crystal structure of the Borrelia burgdorferi nicotinamidase BBE22 resolves a long-standing annotation error","authors":"Kalvis Brangulis","doi":"10.1002/2211-5463.70268","DOIUrl":"10.1002/2211-5463.70268","url":null,"abstract":"Nicotinamidases (PncA) catalyze the hydrolysis of nicotinamide to nicotinic acid, a key step in NAD+ salvage pathways. In the Lyme disease spirochete Borrelia burgdorferi, the plasmid-encoded gene bbe22 encodes a PncA enzyme that is essential for survival in both mammalian and tick hosts. Previous genetic and biochemical studies demonstrated that translation of B. burgdorferi PncA initiates from a rare non-canonical AUU start codon, resulting in a protein that is 24 residues longer than the sequence currently annotated in major databases. Despite these findings, public resources such as UniProt and KEGG still list a truncated protein beginning at residue 36, which lacks part of the N-terminal region required for enzymatic activity. Here we report the crystal structure of full-length B. burgdorferi PncA determined at 3.2 Å resolution. The structure reveals the canonical fold of bacterial nicotinamidases and clear electron density for a ligand in the active site consistent with nicotinic acid, the product of the enzymatic reaction. Structural comparison with homologous PncA enzymes demonstrates conservation of the catalytic architecture, including residues involved in substrate binding and catalysis. Importantly, the experimentally determined structure confirms that the longer N-terminal sequence described previously is required for formation of the correct fold and active-site geometry, whereas the truncated annotation is structurally inconsistent with the observed fold and with AlphaFold predictions. Our results provide the first structural characterization of B. burgdorferi PncA and resolve the long-standing annotation discrepancy for bbe22, validating the correct protein sequence and providing the structural basis for nicotinamidase activity in this essential metabolic enzyme.","PeriodicalId":12187,"journal":{"name":"FEBS Open Bio","volume":"16 10","pages":"1974-1981"},"PeriodicalIF":2.7,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13398362/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147873973","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

Optimizing photoexcitation conditions for time-resolved X-ray solution scattering experiments 优化时间分辨x射线溶液散射实验的光激发条件。

IF 2.7 4区生物学

FEBS Open Bio Pub Date : 2026-10-01 Epub Date: 2026-07-15 DOI: 10.1002/2211-5463.70304

Matteo Levantino

引用次数: 0

The C-terminal region of KIF26B is indispensable for nephron progenitor condensation and kidney formation in mice KIF26B的c端区域是小鼠肾素祖细胞凝聚和肾脏形成所不可缺少的。

IF 2.7 4区生物学

FEBS Open Bio Pub Date : 2026-10-01 Epub Date: 2026-05-18 DOI: 10.1002/2211-5463.70260

Yuta Yamamura, Kengo Furuichi, Hiromitsu Akamatsu, Naoki Yamamoto, Sako Keisuke, Akihiko Koshino, Taichiro Minami, Megumi Oshima, Akinori Hara, Norihiko Sakai, Miho Shimizu, Kenta Takahashi, Minako Yamamura, Shin-ichi Horike, Takiko Daikoku, Kenichi Harada, Yohei Shinmyo, Hiroshi Kawasaki, Takashi Wada, Yasunori Iwata

{"title":"The C-terminal region of KIF26B is indispensable for nephron progenitor condensation and kidney formation in mice","authors":"Yuta Yamamura, Kengo Furuichi, Hiromitsu Akamatsu, Naoki Yamamoto, Sako Keisuke, Akihiko Koshino, Taichiro Minami, Megumi Oshima, Akinori Hara, Norihiko Sakai, Miho Shimizu, Kenta Takahashi, Minako Yamamura, Shin-ichi Horike, Takiko Daikoku, Kenichi Harada, Yohei Shinmyo, Hiroshi Kawasaki, Takashi Wada, Yasunori Iwata","doi":"10.1002/2211-5463.70260","DOIUrl":"10.1002/2211-5463.70260","url":null,"abstract":"Loss of Kif26b function causes renal agenesis or hypoplasia in mice, and a KIF26B mutation resulting in deletion of the C-terminal region has been identified in a human patient with a congenital kidney disorder. However, the role of this region during kidney development is unclear; thus, to investigate this, we generated mice lacking the C-terminal region of KIF26B (Kif26b-C) using CRISPR/Cas9. Homozygous Kif26b-C mice showed bilateral renal agenesis, resembling Kif26b knockout mice. Histological analysis revealed loss of the nephrogenic zone and impaired nephron progenitor condensation at embryonic day 18.5. In situ hybridization showed reduced Gdnf in the metanephric mesenchyme and reduced Wnt11 in ureteric buds, indicating disruption of the Gdnf-Wnt11 signaling loop. These findings suggest a key role for the KIF26B C-terminal region in kidney morphogenesis.","PeriodicalId":12187,"journal":{"name":"FEBS Open Bio","volume":"16 10","pages":"1925-1933"},"PeriodicalIF":2.7,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13398707/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147971892","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

KDAC6 alters cell morphology and motility through positive and negative modulation of F-actin distribution. KDAC6通过正、负调节f -肌动蛋白分布改变细胞形态和运动。

IF 2.7 4区生物学

FEBS Open Bio Pub Date : 2026-09-25 DOI: 10.1002/2211-5463.70302

Taylor V Joseph, Andrea B Pham, Kiara E Bornes, Razan H Hammad, Chelsea A Rousseve-Ross, Thomas M Huckaba, Terry J Watt, Tasha B Toro

{"title":"KDAC6 alters cell morphology and motility through positive and negative modulation of F-actin distribution.","authors":"Taylor V Joseph, Andrea B Pham, Kiara E Bornes, Razan H Hammad, Chelsea A Rousseve-Ross, Thomas M Huckaba, Terry J Watt, Tasha B Toro","doi":"10.1002/2211-5463.70302","DOIUrl":"10.1002/2211-5463.70302","url":null,"abstract":"Lysine deacetylase 6 (KDAC6 or HDAC6) has been associated with cell motility and deacetylation of cytoskeleton-related proteins. KDAC6 is the only human KDAC having three identified major domains, including two catalytic domains (CD). Defining the roles of KDAC6 in cell motility has been constrained by limited understanding of domain-specific contributions. Live and fixed cell imaging was used to characterize the effects of KDAC6 on F-actin distribution, cell morphology, and cell motility of genetically modified HT1080 cells containing KDAC6 with an inactivated CD or knockout. CD1 inactivation resulted in cells that migrated faster and had more concentrated cortical F-actin at the leading edge. Conversely, inactivation of CD2 resulted in slower migration, depleted cortical F-actin, more stress fibers with poor alignment, and larger, flatter cells. Loss of both CD1 and CD2 activity in the knockout cell line resulted in phenotypes that were most similar to wild-type cells. Hyperacetylation of α-tubulin alone was insufficient to explain the observed phenotypes of the cell line with inactive CD2, as the knockout cell line had similar hyperacetylation but lacked most of the phenotypic changes. Altered gene expression implicated actin-associated proteins as mediators of phenotypic effects. Although the cell lines exhibited variation in localization of putative KDAC6 targets cortactin and HSP90, these variations did not correlate with the observed phenotypes. Inactivation of CD2 resulted in more focal adhesions formed throughout cells, correlating with more stress fibers and reduced motility. Collectively, these results establish that each CD of KDAC6 has a distinctive and opposing role in F-actin regulation.","PeriodicalId":12187,"journal":{"name":"FEBS Open Bio","volume":" ","pages":""},"PeriodicalIF":2.7,"publicationDate":"2026-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13615371/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149059364","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

TRPML1 agonist ML-SA5 attenuates pulmonary fibroblast activation by suppressing mTOR and restoring autophagic flux. TRPML1激动剂ML-SA5通过抑制mTOR和恢复自噬通量来减弱肺成纤维细胞的激活。

IF 2.7 4区生物学

FEBS Open Bio Pub Date : 2026-09-24 DOI: 10.1002/2211-5463.70346

Jiatong Yao, Xiaoting Kang, Lulu Meng, Shaoxuan Zhang, Qiujie Li, Jinyu Zhou, Mengyue Xue, Chu Li, Hua Zhu, Pengzhou Hang, Jing Zhao

{"title":"TRPML1 agonist ML-SA5 attenuates pulmonary fibroblast activation by suppressing mTOR and restoring autophagic flux.","authors":"Jiatong Yao, Xiaoting Kang, Lulu Meng, Shaoxuan Zhang, Qiujie Li, Jinyu Zhou, Mengyue Xue, Chu Li, Hua Zhu, Pengzhou Hang, Jing Zhao","doi":"10.1002/2211-5463.70346","DOIUrl":"10.1002/2211-5463.70346","url":null,"abstract":"Modulating autophagic processes has shown promise as a treatment for pulmonary fibrosis (PF) with recent studies identifying transient receptor potential mucolipin-1 (TRPML1), a lysosomal ion channel, as a novel regulator involved in PF. However, the mechanism by which TRPML1 modulates autophagy in the context of PF remains incompletely understood. Here we establish in vitro PF models by exposing human embryonic lung fibroblasts (MRC-5) or primary lung fibroblasts to transforming growth factor (TGF-β1). We then assessed the effects of the TRPML1 agonist ML-SA5 on migratory capacity, the levels of fibrosis-related proteins and autophagy markers, and autophagic flux. Our findings show that TGF-β1 stimulation reduced TRPML1 protein levels, while ML-SA5 treatment suppressed TGF-β1-induced cell migration, reduced the expression of fibrotic markers, increased LC3II levels, and restored autophagic flux in lung fibroblasts. Finally, investigating the role of mammalian target of rapamycin (mTOR) signaling in these effects using rapamycin (an mTOR inhibitor) and MHY1485 (an mTOR activator), we found ML-SA5 inhibited mTOR signaling. Specifically, the anti-fibrotic effects of ML-SA5 were enhanced by co-treatment with rapamycin and reversed by MHY1485. Thus, we conclude that ML-SA5 attenuates TGF-β1-induced migration and collagen synthesis in pulmonary fibroblasts, at least in part through suppression of mTOR signaling and restoration of autophagic flux.","PeriodicalId":12187,"journal":{"name":"FEBS Open Bio","volume":" ","pages":""},"PeriodicalIF":2.7,"publicationDate":"2026-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13602826/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149037346","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

The C-terminal truncated splicing variant of NK1R negatively modulates substance P-stimulated NK1R signaling. NK1R的c端截断剪接变体负向调节p物质刺激的NK1R信号。

IF 2.7 4区生物学

FEBS Open Bio Pub Date : 2026-09-21 DOI: 10.1002/2211-5463.70334

Lan Phuong Nguyen, Duc Trung Nguyen, Minyoung Cho, Jihun Kim, Soyeon In, Thai Uy Nguyen, Sunghoon Hurh, Beom Jin Park, Jong-Ik Hwang

引用次数: 0

The C-terminal domain of yeast Arginyltransferase1 is essential for its catalytic activity. 酵母精氨酸基转移酶1的c端结构域对其催化活性至关重要。

IF 2.7 4区生物学

FEBS Open Bio Pub Date : 2026-09-21 DOI: 10.1002/2211-5463.70336

Vikas Kumar Yadav, Shweta Shweta, Manisha Malhotra, Vikash Maurya, Akhilesh Kumar

{"title":"The C-terminal domain of yeast Arginyltransferase1 is essential for its catalytic activity.","authors":"Vikas Kumar Yadav, Shweta Shweta, Manisha Malhotra, Vikash Maurya, Akhilesh Kumar","doi":"10.1002/2211-5463.70336","DOIUrl":"10.1002/2211-5463.70336","url":null,"abstract":"Arginyltransferase 1 (Ate1), a conserved eukaryotic enzyme, has recently been structurally characterised; identifying a conserved N-terminal domain, a central GNAT fold and a variable C-terminal domain of unknown function. Here, using budding yeast as an experimental model, we established that the C-terminal domain is indispensable for Ate1 stability, its enzymatic activity and Ate1-mediated cell death. Furthermore, we found that the co-expression of separated N-terminal and C-terminal halves of Ate1 did not reconstitute enzyme activity in vivo. Also, we observed that the mutation of conserved residues involved in cofactor binding and active site formation within the N-terminal half of Ate1 abolishes the enzyme function. Moreover, we showed that mouse Ate1, when heterogeneously expressed in yeast, was catalytically active but not lethal. These findings underscore the structural interdependence of Ate1 domains and their integrity in maintaining enzyme catalytic activity and stability, providing deeper insights into the enzyme structure-function relationship.","PeriodicalId":12187,"journal":{"name":"FEBS Open Bio","volume":" ","pages":""},"PeriodicalIF":2.7,"publicationDate":"2026-09-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13592012/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149012536","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