Biochimica et biophysica acta. Molecular cell research最新文献_第2页

Insights from Interleukin-6 trans-signaling and implications for the control of cytokine activity 白细胞介素-6反式信号传导及其对细胞因子活性控制的意义。

IF 3.7 2区生物学

Biochimica et biophysica acta. Molecular cell research Pub Date : 2026-03-01 Epub Date: 2026-01-09 DOI: 10.1016/j.bbamcr.2026.120109

Stefan Rose-John

引用次数: 0

Understanding complex formation of gp130 cytokines for the design of selective therapeutics 了解gp130细胞因子的复杂形成以设计选择性疗法。

IF 3.7 2区生物学

Biochimica et biophysica acta. Molecular cell research Pub Date : 2026-03-01 Epub Date: 2026-01-05 DOI: 10.1016/j.bbamcr.2026.120105

Isabel Ramón Roth , Jana I. Führing , Christoph Garbers

{"title":"Understanding complex formation of gp130 cytokines for the design of selective therapeutics","authors":"Isabel Ramón Roth , Jana I. Führing , Christoph Garbers","doi":"10.1016/j.bbamcr.2026.120105","DOIUrl":"10.1016/j.bbamcr.2026.120105","url":null,"abstract":"<div><div>Cytokines activate their target cells via binding to specific receptors on the cell surface. The receptor glycoprotein 130 (gp130) is ubiquitously expressed throughout the human body and used by nine members of the interleukin-6 (IL-6) family of cytokines to facilitate the initiation of intracellular signalling cascades. Although these cytokines share the same protein fold, gp130 requires substantial promiscuity in order to bind such diverse proteins. In this review, we summarize what is currently known about the structural features of gp130 that allow this flexibility towards its binding partners. We compare this to the other non-signalling α-receptors and signal-transducing β-receptors of the family and discuss how IL-6 family cytokines form signalling complexes at the cell surface that lead to the activation of intracellular signalling cascades. We further show how mutations found in human patients influence gp130 signalling, and describe how such knowledge can be used to create tailor-made designer proteins that can be used as next-generation therapeutics for the treatment of inflammatory diseases.</div></div>","PeriodicalId":8754,"journal":{"name":"Biochimica et biophysica acta. Molecular cell research","volume":"1873 3","pages":"Article 120105"},"PeriodicalIF":3.7,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145916918","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

Cyclin dependent kinases CDK8/19 are required for PKA inactivation during meiosis resumption 细胞周期蛋白依赖激酶CDK8/19是PKA在减数分裂恢复过程中失活所必需的。

IF 3.7 2区生物学

Biochimica et biophysica acta. Molecular cell research Pub Date : 2026-03-01 Epub Date: 2026-01-17 DOI: 10.1016/j.bbamcr.2026.120114

Yulia Okulova , Maxim Filatov , Ekaterina Varlamova , Anna Tvorogova , Evgeniy Korshunov , Yulia Silaeva , Victor Tatarskiy , Alexandra Bruter

{"title":"Cyclin dependent kinases CDK8/19 are required for PKA inactivation during meiosis resumption","authors":"Yulia Okulova , Maxim Filatov , Ekaterina Varlamova , Anna Tvorogova , Evgeniy Korshunov , Yulia Silaeva , Victor Tatarskiy , Alexandra Bruter","doi":"10.1016/j.bbamcr.2026.120114","DOIUrl":"10.1016/j.bbamcr.2026.120114","url":null,"abstract":"<div><div>CDK8/19 are transcriptional cyclin dependent kinases, which do not directly control cell cycle progression. CDK8/19 are involved in regulation of multiple processes in embryogenesis, cancer progression, immune activation and others. Previously we demonstrated that CDK8/19 are critical for spermatogenesis in mice. Here we report that CDK8/19 activity is also required for oocyte maturation playing a significant role in meiosis resumption in mouse oocytes. Two chemically distinct CDK8/19 inhibitors – Senexin B and Snx631 prevented nuclear envelope breakdown and first polar body extrusion, blocking key molecular events required for exiting the dictyate - inhibition of PKA activity and activation of the CDK1/Cyclin B complex. This effect did not cause cytotoxicity, and oocytes could resume progression upon transfer into fresh media. Inhibition of CDK8/19 also prevented meiotic-specific mitochondrial expansion and clustering. Notably, these effects appear to be independent of roles of CDK8/19 in transcription, which is not required for resumption of meiosis. These findings for the first time demonstrate the roles of CDK8/19 activity in oocyte maturation, through its role in transcription-independent regulation of PKA activity.</div></div>","PeriodicalId":8754,"journal":{"name":"Biochimica et biophysica acta. Molecular cell research","volume":"1873 3","pages":"Article 120114"},"PeriodicalIF":3.7,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146002960","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

Insights into the regulation and signaling landscape of cardiotrophin-like cytokine factor 1 (CLCF1) 心肌营养因子样细胞因子1 （CLCF1）的调控和信号转导研究。

IF 3.7 2区生物学

Biochimica et biophysica acta. Molecular cell research Pub Date : 2026-03-01 Epub Date: 2026-02-07 DOI: 10.1016/j.bbamcr.2026.120123

Marine Rousseau , France Côté , Sylvain Chemtob , Jean-François Gauchat , Sarah Pasquin , Sylvie Lesage

{"title":"Insights into the regulation and signaling landscape of cardiotrophin-like cytokine factor 1 (CLCF1)","authors":"Marine Rousseau , France Côté , Sylvain Chemtob , Jean-François Gauchat , Sarah Pasquin , Sylvie Lesage","doi":"10.1016/j.bbamcr.2026.120123","DOIUrl":"10.1016/j.bbamcr.2026.120123","url":null,"abstract":"<div><div>Cardiotrophin-like cytokine factor 1 (CLCF1) is an essential gene that shows exceptional sequence conservation among vertebrates. <em>CLCF1</em> loss-of-function mutations cause Crisponi/cold-induced sweating syndrome-2, a disorder with severe and complex phenotypes, underscoring the non-redundant roles of CLCF1. Initially identified as a member of the interleukin-6 (IL-6) cytokine family with activity in neurons and immune cells, CLCF1 is now recognized for broader roles in thermoregulation, glomerular function, myelopoiesis, oncogenesis, and muscle fitness. Despite growing interest in the multifaceted biology of CLCF1, the mechanisms regulating its transcription, translation, secretion, receptor binding, and signaling remain incompletely understood. This review integrates data from multiple open databases and functional studies to outline the current state of knowledge regarding CLCF1 regulatory landscape, receptor interactions, and downstream signaling. It also highlights recent discoveries about the CLCF1 interactome and intracellular functions and underlines its emerging potential as a therapeutic target.</div></div>","PeriodicalId":8754,"journal":{"name":"Biochimica et biophysica acta. Molecular cell research","volume":"1873 3","pages":"Article 120123"},"PeriodicalIF":3.7,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146148935","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

Mutant-specific dysfunction of RHOBTB2 impairs mitochondrial function and Na+/K+-ATPase levels in a cell model 在细胞模型中，RHOBTB2突变特异性功能障碍损害线粒体功能和Na+/K+- atp酶水平

IF 3.7 2区生物学

Biochimica et biophysica acta. Molecular cell research Pub Date : 2026-03-01 Epub Date: 2025-12-31 DOI: 10.1016/j.bbamcr.2025.120103

Sachiko Miyamoto , Shun-ichi Yamashita , Hazrat Belal , Mitsuhiro Kato , Tomotake Kanki , Hirotomo Saitsu

{"title":"Mutant-specific dysfunction of RHOBTB2 impairs mitochondrial function and Na+/K+-ATPase levels in a cell model","authors":"Sachiko Miyamoto , Shun-ichi Yamashita , Hazrat Belal , Mitsuhiro Kato , Tomotake Kanki , Hirotomo Saitsu","doi":"10.1016/j.bbamcr.2025.120103","DOIUrl":"10.1016/j.bbamcr.2025.120103","url":null,"abstract":"<div><div><em>RHOBTB2</em> is an atypical Rho GTPase implicated in developmental and epileptic encephalopathy, yet its pathogenic mechanisms remain poorly understood. In this study, we established a cell model in which <em>RHOBTB2</em> expression was induced by a doxycycline-inducible system to investigate the functional consequences of disease-associated <em>RHOBTB2</em> mutants. Protein expression and localization analyses revealed mutant-specific behaviors: GTPase-domain mutants such as D92H and W217C showed no significant difference in RHOBTB2 protein levels compared with WT, while hotspot mutants (R461H, R485C, R489Q) exhibited increased RHOBTB2 protein levels with nuclear and mitochondrial accumulation. RNA-seq analysis revealed that cells expressing each mutant showed distinct transcriptomic changes. Notably, induction of the R489Q mutant caused a robust downregulation of ion channel-related genes, supporting its potential role in disrupting neuronal excitability. Furthermore, expression of mutant RHOBTB2 led to a reduction in Na<sup>+</sup>/K<sup>+</sup>-ATPase protein levels via a lysosome-dependent degradation pathway. This effect was particularly prominent in GTPase-domain mutants (D92H and W217C), suggesting a mechanistic link between mutant RHOBTB2 and impaired ion homeostasis. Moreover, the R489Q and W217C mutants impaired mitochondrial respiration, whereas other mutants did not show detectable mitochondrial dysfunction. Importantly, the Y284D cancer-associated mutant did not share these phenotypes, highlighting the diversity of functional outcomes across different mutation sites. The observed dysregulation of ion transport pathways and mitochondrial impairment in some mutants may represent key mechanisms underlying seizure susceptibility and other neurological manifestations in <em>RHOBTB2</em>-associated encephalopathies.</div></div>","PeriodicalId":8754,"journal":{"name":"Biochimica et biophysica acta. Molecular cell research","volume":"1873 3","pages":"Article 120103"},"PeriodicalIF":3.7,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145883665","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

Friend or foe: New cytokine players in beta cell failure in type 1 diabetes mellitus 是敌是友：1型糖尿病β细胞衰竭的新细胞因子。

IF 3.7 2区生物学

Biochimica et biophysica acta. Molecular cell research Pub Date : 2026-03-01 Epub Date: 2026-01-19 DOI: 10.1016/j.bbamcr.2026.120113

Ewa Gurgul-Convey, Ortwin Naujok

引用次数: 0

The language of cytokines: Decoding immune signals with information theory 细胞因子的语言：用信息论解码免疫信号。

IF 3.7 2区生物学

Biochimica et biophysica acta. Molecular cell research Pub Date : 2026-03-01 Epub Date: 2026-01-22 DOI: 10.1016/j.bbamcr.2026.120119

Sophie Streuber , Emelie Rieneck , Fred Schaper , Anna Dittrich

{"title":"The language of cytokines: Decoding immune signals with information theory","authors":"Sophie Streuber , Emelie Rieneck , Fred Schaper , Anna Dittrich","doi":"10.1016/j.bbamcr.2026.120119","DOIUrl":"10.1016/j.bbamcr.2026.120119","url":null,"abstract":"<div><div>Communication between cells is fundamental for maintaining and restoring homeostasis in multicellular organisms under both physiological and pathological conditions. A variety of mechanisms for encoding, transmitting, and decoding information have evolved. Information theory, originally developed in engineering, has been increasingly applied to dissect how cells process and exchange signals. Yet, biological systems exhibit distinctive properties that pose conceptual and quantitative challenges not encountered in technical systems. In this review, we examine how cellular networks manage and often exploit the intrinsic heterogeneity of cell populations. We discuss how individual cells and cell populations sense cytokine stimulus strength and specificity, and how regulatory proteins shape not only signalling dynamics but also the capacity and robustness of information transmission. From an information theoretical perspective, health can be viewed as a state of efficient and reliable cellular communication, whereas disease reflects the loss or distortion of robust cellular communication. We conclude that information theory offers an intuitive framework for biologists seeking to unravel the principles of cytokine signalling.</div></div>","PeriodicalId":8754,"journal":{"name":"Biochimica et biophysica acta. Molecular cell research","volume":"1873 3","pages":"Article 120119"},"PeriodicalIF":3.7,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146043576","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

Development of a TEAD-independent reporter system for specific and sensitive measurement of YAP/TAZ activity 开发一个独立于tead的报告系统，用于特异性和敏感性测量YAP/TAZ活性

IF 3.7 2区生物学

Biochimica et biophysica acta. Molecular cell research Pub Date : 2026-03-01 Epub Date: 2026-01-12 DOI: 10.1016/j.bbamcr.2026.120111

Jiuge Zhang , Wenqian Yang , Qiuyun Yuan , Fei Huang , Die Lv , Yixin Zhang , Xiaoqiang Xia , Yuan Yue , Xiaodong Feng

{"title":"Development of a TEAD-independent reporter system for specific and sensitive measurement of YAP/TAZ activity","authors":"Jiuge Zhang , Wenqian Yang , Qiuyun Yuan , Fei Huang , Die Lv , Yixin Zhang , Xiaoqiang Xia , Yuan Yue , Xiaodong Feng","doi":"10.1016/j.bbamcr.2026.120111","DOIUrl":"10.1016/j.bbamcr.2026.120111","url":null,"abstract":"<div><div>Accurate quantification of Yes-associated protein (YAP) and its paralog TAZ is critical for understanding their biological functions, however, existing reporter systems are constrained by their reliance on endogenous TEAD transcription factors. Here, we developed an endogenous TEAD-independent reporter system for YAP/TAZ activity, based on the GAL4-UAS system. The construct consists of the GAL4 DNA-binding domain (DBD) fused to the YAP-binding domain (YBD) of TEAD4, with the native TEAD DNA-binding domain (TEA) removed. Structural modeling of the G-TEAD4(217) fusion protein confirmed high similarity to experimentally resolved TEAD4-YAP or GAL4-DNA bound structures and revealed surface properties consistent with functional domain separation. Functional assays showed that the reporter reliably responded to both YAP knockdown and overexpression. Compared to the conventional 8 × GTIIC reporter, G-TEAD4(217) exhibited higher sensitivity and remained unaffected by TEAD4 silencing, confirming reporter specificity and TEAD independence. In addition, the system demonstrated its suitability for compound screening by validating known YAP inhibitors across a number of high-YAP cancer cell lines. A single-plasmid lentiviral version LV-G-TEAD4(217) was also developed to enable stable transduction and potential in vivo use. Together, these findings demonstrate that G-TEAD4(217) represents a sensitive, specific, and modular reporter platform for analyzing YAP/TAZ transcriptional activity in diverse biological settings.</div></div>","PeriodicalId":8754,"journal":{"name":"Biochimica et biophysica acta. Molecular cell research","volume":"1873 3","pages":"Article 120111"},"PeriodicalIF":3.7,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145974086","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 endocytic fission protein EHD1 interacts with tubulin and regulates microtubule function 内吞裂变蛋白EHD1与微管蛋白相互作用并调节微管功能。

IF 3.7 2区生物学

Biochimica et biophysica acta. Molecular cell research Pub Date : 2026-03-01 Epub Date: 2026-01-27 DOI: 10.1016/j.bbamcr.2026.120120

Bazella Ashraf , Journey Reddick-Umoja , Jasmyn Grant , Jyoti Iyer , Naava Naslavsky , Steve Caplan

{"title":"The endocytic fission protein EHD1 interacts with tubulin and regulates microtubule function","authors":"Bazella Ashraf , Journey Reddick-Umoja , Jasmyn Grant , Jyoti Iyer , Naava Naslavsky , Steve Caplan","doi":"10.1016/j.bbamcr.2026.120120","DOIUrl":"10.1016/j.bbamcr.2026.120120","url":null,"abstract":"<div><div>The Eps15 Homology Domain protein-1 (EHD1) is an ATPase and key endocytic regulatory protein required for optimal receptor recycling, and primary ciliogenesis. Over the past decade, a central role for EHD1 has been identified in the fission of endosomes. Despite these findings, additional evidence has also pointed at a potential function of EHD1 in the regulation of microtubules. Herein, we demonstrate that EHD1 regulates the distribution of endosomes, and conversely, centrosome depletion alters EHD1 localization in cells. We show that endogenous EHD1 is found in a complex with various endogenous tubulins including TUBB3, TUBB1, α-tubulin and γ-tubulin, interactions that are independent of intact microtubules, and appear to be indirect. Depletion of key individual EHD1 interaction partners that are known to bind tubulin fail to impede EHD1-tubulin interactions, suggesting that either several proteins are capable of mediating EHD1's connection with microtubules, or that the bridging interaction partner remains to be identified. Functionally, EHD1 depletion leads to impaired microtubule regrowth and decreased end-binding protein displacement, suggesting a role for EHD1 in modulating microtubule plus-end dynamics. Finally, EHD1's role in microtubule regulation appears to be evolutionarily conserved, as single-cell stage <em>C. elegans</em> embryos with a dysfunctional EHD1/RME-1 protein displayed enhanced tubulin accumulation at metaphase spindle poles. Our findings strongly support a previously unaddressed role for EHD1 in microtubule regulation.</div></div>","PeriodicalId":8754,"journal":{"name":"Biochimica et biophysica acta. Molecular cell research","volume":"1873 3","pages":"Article 120120"},"PeriodicalIF":3.7,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146083933","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

Regulation of E-cadherin by mixed lineage kinase 3 (MLK3) mediates cell adhesion in ovarian cancer spheroids 混合谱系激酶3 （MLK3）调控e -钙粘蛋白介导卵巢癌球体细胞粘附

IF 3.7 2区生物学

Biochimica et biophysica acta. Molecular cell research Pub Date : 2026-03-01 Epub Date: 2026-01-07 DOI: 10.1016/j.bbamcr.2026.120106

Mariah C.J. Rozier, Danielle N. Adjei, Rachel A. Radtke, Deborah N. Chadee

{"title":"Regulation of E-cadherin by mixed lineage kinase 3 (MLK3) mediates cell adhesion in ovarian cancer spheroids","authors":"Mariah C.J. Rozier, Danielle N. Adjei, Rachel A. Radtke, Deborah N. Chadee","doi":"10.1016/j.bbamcr.2026.120106","DOIUrl":"10.1016/j.bbamcr.2026.120106","url":null,"abstract":"<div><div>Mixed lineage kinase 3 (MLK3) is a serine/threonine mitogen-activated protein kinase (MAPK) kinase kinase (MAP3K) that activates MAPK signaling pathways and promotes cell proliferation, migration and invasion. E-cadherin is an essential cell adhesion protein that mediates cell-cell interactions in epithelial adherens junctions and is crucial for the integrity of tissues and organs. Here, we demonstrate that MLK3 siRNA knockdown or kinase inhibition significantly impaired spheroid formation in SKOV3, TOV112D and OVCAR3 ovarian cancer cells, that was rescued by overexpression of E-cadherin. Endogenous MLK3 and E-cadherin were co-immunoprecipitated from ovarian cancer cell lysates; and recombinant MLK3 and E-cadherin directly interacted <em>in vitro</em>. MLK3 phosphorylates E-cadherin and has a positive regulatory effect on E-cadherin protein stability. Like E-cadherin, MLK3 is localized to the plasma membrane at regions of cell-cell contact, and MLK3 also has cytoplasmic and nuclear localization. Neither the MLK3-E-cadherin interaction nor the plasma membrane localization of MLK3 is dependent on β-catenin. Collectively, these results indicate a novel function for MLK3 in regulating E-cadherin protein stability, cell adhesion, and ovarian cancer spheroid formation.</div></div>","PeriodicalId":8754,"journal":{"name":"Biochimica et biophysica acta. Molecular cell research","volume":"1873 3","pages":"Article 120106"},"PeriodicalIF":3.7,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145923181","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