Advances in biological regulation最新文献_第3页

Potential endogenous lipid ligands for the nuclear receptor transcription factor Steroidogenic Factor-1 潜在的内源性脂质配体为核受体转录因子甾体生成因子-1。

IF 2.4

Advances in biological regulation Pub Date : 2026-01-01 Epub Date: 2025-11-12 DOI: 10.1016/j.jbior.2025.101131

Alexis N. Campbell , Raymond D. Blind

{"title":"Potential endogenous lipid ligands for the nuclear receptor transcription factor Steroidogenic Factor-1","authors":"Alexis N. Campbell , Raymond D. Blind","doi":"10.1016/j.jbior.2025.101131","DOIUrl":"10.1016/j.jbior.2025.101131","url":null,"abstract":"<div><div>Nuclear receptors are lipid-regulated transcription factors that respond to the changing metabolic and signaling requirements of animal cells and tissues. Steroidogenic Factor 1 (SF-1, <em>NR5A1</em>) is a nuclear receptor and master regulator of steroidogenic gene expression. SF-1 is required for development and adult function of steroidogenic tissues, hyperactivation of SF-1 associates with adrenocortical carcinoma, while hypomorphic loss-of-function polymorphisms associate with disorders of sexual development. Many of these physiological functions of SF-1 are broadly understood, however the identity of the endogenous regulatory lipid ligands for SF-1 have yet to be well established, preventing progress on therapeutic development for human diseases, such as adrenocortical carcinoma. Several signaling lipids have been put forth as potential regulatory ligands of SF-1, including sphingosine, lyso-sphingomyelin, sphingomyelin, ceramide and several phosphoinositide species including PI(4,5)P2 and PI(3,4,5)P3. Here, we review the evidence linking the ability of these potential phospholipid ligands to regulate SF-1 mediated gene expression in metazoan cells, and discuss how lipid ligands regulate SF-1 from a structural perspective.</div></div>","PeriodicalId":7214,"journal":{"name":"Advances in biological regulation","volume":"99 ","pages":"Article 101131"},"PeriodicalIF":2.4,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145533867","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Activity and dynamics of p110α are not differentially modulated by regulatory subunit isoforms p110α的活性和动态不受调节亚基异构体的差异调节。

IF 2.4

Advances in biological regulation Pub Date : 2026-01-01 Epub Date: 2025-11-04 DOI: 10.1016/j.jbior.2025.101128

Isobel Barlow-Busch , Emma E. Walsh , Hunter G. Nyvall , John E. Burke

{"title":"Activity and dynamics of p110α are not differentially modulated by regulatory subunit isoforms","authors":"Isobel Barlow-Busch , Emma E. Walsh , Hunter G. Nyvall , John E. Burke","doi":"10.1016/j.jbior.2025.101128","DOIUrl":"10.1016/j.jbior.2025.101128","url":null,"abstract":"<div><div>Class IA phosophoinositide kinases (PI3Ks) are master regulators of growth, metabolism, and immunity. The class IA PI3Ks are a heterodimer composed of a p110 catalytic subunit and one of five possible regulatory subunits (p85α, p85β, p55γ, p55α, p50α). The regulatory subunit plays critical roles in stability, inhibition, and activation of the p110 catalytic subunit. The p110α catalytic subunit frequently contains activating mutations in human cancer, with many of these mutations altering the interaction between catalytic and regulatory subunits. It has been found that different regulatory subunits play unique roles in human disease, but it is unknown how these different subunits regulate p110α. Here, using a synergy of biochemical assays and hydrogen deuterium exchange mass spectrometry (HDX-MS) we examined how the five different regulatory subunits inhibit, activate, and interact with the p110α catalytic subunit. We find that there are no significant differences in lipid kinase activity or in membrane recruitment between the different heterodimer complexes. HDX-MS in the presence and absence of an activating phosphopeptide also showed only minor conformational differences between different regulatory subunit complexes. Overall, our work reveals that the different regulatory subunits interact with and inhibit p110α in a similar fashion at a molecular level.</div></div>","PeriodicalId":7214,"journal":{"name":"Advances in biological regulation","volume":"99 ","pages":"Article 101128"},"PeriodicalIF":2.4,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145470288","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Inositide-dependent signal transduction in the nucleus: a virtuous path from the laboratory to the clinic 核中肌苷依赖的信号转导：从实验室到临床的良性途径。

IF 2.4

Advances in biological regulation Pub Date : 2026-01-01 Epub Date: 2025-12-10 DOI: 10.1016/j.jbior.2025.101142

Alessia De Stefano , James A. McCubrey , Pann-Ghill Suh , Giulia Ramazzotti , Roberta Fiume , Stefano Ratti , Matilde Y. Follo , Lucia Manzoli , Lucio Cocco

引用次数: 0

Phosphatidic acid at the crossroads of membrane dynamics: from molecular specificity to synthetic innovation 磷脂酸在膜动力学的十字路口：从分子特异性到合成创新。

IF 2.4

Advances in biological regulation Pub Date : 2026-01-01 Epub Date: 2025-10-25 DOI: 10.1016/j.jbior.2025.101123

Alexander Wolf, Emeline Tanguy, Stéphane Gasman, Nicolas Vitale

{"title":"Phosphatidic acid at the crossroads of membrane dynamics: from molecular specificity to synthetic innovation","authors":"Alexander Wolf, Emeline Tanguy, Stéphane Gasman, Nicolas Vitale","doi":"10.1016/j.jbior.2025.101123","DOIUrl":"10.1016/j.jbior.2025.101123","url":null,"abstract":"<div><div>Phosphatidic acid (PA) has emerged as a central regulator of membrane dynamics, vesicle trafficking, exocytosis, and intracellular signaling. Building on recent advances, including subspecies-specific functions of PA in neuroendocrine exocytosis, the primacy of PLD1-derived PA <em>in vivo</em>, and the development of natural-mimetic PA analogues, this review integrates biochemical, biophysical, and systems-level insights across eukaryotes. We contextualize the role of PA in vesicular trafficking, delineate how acyl-chain composition encodes molecular specificity, summarize enzymatic sources and sinks sculpting spatiotemporal control of PA pools within cells, and examine emerging tools used for measuring and disturbing PA in living cells to unravel its function. Given the pleiotropic roles of PA among numerous experimental contexts such as the nervous, endocrine, immune, and metabolic systems, mapping mechanistic connections to disease through mTOR and RAF/MEK/ERK signaling, autophagy, and organelle contact-site biology. Finally, we outline future directions spanning single-cell lipidomics, imaging mass spectrometry, and therapeutic lipid engineering. Together, available evidence positions PA as a conserved, tunable molecular switch that coordinates membrane mechanics with signal transduction to enable realisation of a wide range of function within cells.</div></div>","PeriodicalId":7214,"journal":{"name":"Advances in biological regulation","volume":"99 ","pages":"Article 101123"},"PeriodicalIF":2.4,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145420929","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Conventional and alternative approaches for targeting PIK3CA and PTEN alterations in head and neck, breast, and other cancers 靶向头颈部、乳腺癌和其他癌症中PIK3CA和PTEN改变的常规和替代方法

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Advances in biological regulation Pub Date : 2026-01-01 Epub Date: 2025-09-26 DOI: 10.1016/j.jbior.2025.101117

Jovanka Gencel-Augusto, Jennifer R. Grandis, Daniel E. Johnson

引用次数: 0

The AP-4 accessory protein tepsin exhibits multivalent binding to LC3B AP-4辅助蛋白蛋白酶与LC3B具有多价结合。

IF 2.4

Advances in biological regulation Pub Date : 2026-01-01 Epub Date: 2025-10-27 DOI: 10.1016/j.jbior.2025.101124

Cameron I. Cohen , Amy K. Kendall , Natalie S. Wallace , Maggie L. McCorkle , Lauren P. Jackson

{"title":"The AP-4 accessory protein tepsin exhibits multivalent binding to LC3B","authors":"Cameron I. Cohen , Amy K. Kendall , Natalie S. Wallace , Maggie L. McCorkle , Lauren P. Jackson","doi":"10.1016/j.jbior.2025.101124","DOIUrl":"10.1016/j.jbior.2025.101124","url":null,"abstract":"<div><div>Tepsin is an accessory protein in Adaptor Protein 4 (AP-4) coated vesicles responsible for trafficking cargo from the <em>trans</em>-Golgi network (TGN). AP-4 vesicles recognize and sort multiple cargoes including ATG9A, a lipid scramblase essential for autophagosome maturation. In cultured cells, tepsin loss alters ATG9A distribution and autophagosome morphology, and tepsin has been shown to contain a canonical LC3-interacting region (LIR) motif required for proper ATG9A distribution. Computational modeling in AlphaFold Multimer combined with biochemical and biophysical experiments identified three additional LC3B binding motifs within tepsin disordered regions. Structural models paired with bio-layer interferometry (BLI) uncovered and confirmed specific residues involved in each interaction and indicated all four motifs independently engage the LC3B LIR docking site (LDS). Thermodynamic and kinetic properties associated with each motif found in full-length tepsin were quantified. BLI and biochemical data reveal all four motifs in tepsin must be mutated to abrogate binding to LC3B <em>in vitro</em>, while stoichiometry data estimate one tepsin likely binds two LC3B at one time on a surface or membrane. Together, data suggest tepsin could respond dynamically to LC3B concentrations on membranes by leveraging multivalency to modulate binding strength.</div></div>","PeriodicalId":7214,"journal":{"name":"Advances in biological regulation","volume":"99 ","pages":"Article 101124"},"PeriodicalIF":2.4,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145457281","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Unveiling the role of biomolecular condensates in cellular function and cancer 揭示生物分子凝聚物在细胞功能和癌症中的作用

IF 2.4

Advances in biological regulation Pub Date : 2025-12-01 Epub Date: 2025-09-03 DOI: 10.1016/j.jbior.2025.101105

Herencia-Lagunar Elena , Carrera-Bravo Claudia , Castano Enrique , Sztacho Martin

{"title":"Unveiling the role of biomolecular condensates in cellular function and cancer","authors":"Herencia-Lagunar Elena , Carrera-Bravo Claudia , Castano Enrique , Sztacho Martin","doi":"10.1016/j.jbior.2025.101105","DOIUrl":"10.1016/j.jbior.2025.101105","url":null,"abstract":"<div><div>Biomolecular condensates (BMCs) are membrane-less organelles formed through liquid-liquid phase separation, primarily driven by multivalent interactions between scaffold and client molecules. These dynamic compartments enable cells to spatially and temporally organize biochemical reactions by locally concentrating specific biomolecules, thereby enhancing the frequency of productive molecular interactions and increasing reaction rates. BMCs are integral to normal cellular physiology, with well-characterized examples including the nucleolus and Cajal bodies. However, aberrant formation or regulation of condensates has been implicated in the pathogenesis of several diseases, including neurodegenerative disorders, cancer, and immune-related conditions. Intrinsically disordered regions and disease-associated mutations in key residues often promote pathological phase separation, contributing to condensate dysregulation. A comprehensive understanding of the molecular principles governing BMC biogenesis is critical for the development of novel, non-invasive therapeutic strategies aimed at modulating condensate dynamics in disease contexts.</div></div>","PeriodicalId":7214,"journal":{"name":"Advances in biological regulation","volume":"98 ","pages":"Article 101105"},"PeriodicalIF":2.4,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144997408","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

The role of glycolytic condensates in the cellular stress response during cancer progression 糖酵解凝聚物在癌症进展过程中细胞应激反应中的作用

IF 2.4

Advances in biological regulation Pub Date : 2025-12-01 Epub Date: 2025-08-29 DOI: 10.1016/j.jbior.2025.101104

Elena Herencia-Lagunar, Claudia Carrera-Bravo, Martin Sztacho

引用次数: 0

DNA intercalating drugs: Mechanisms of action in cancer treatment DNA嵌入药物：在癌症治疗中的作用机制。

IF 2.4

Advances in biological regulation Pub Date : 2025-12-01 Epub Date: 2025-09-24 DOI: 10.1016/j.jbior.2025.101115

Marvellous Oyeyode , Mathew Tempel , Ted M. Lakowski , James R. Davie

{"title":"DNA intercalating drugs: Mechanisms of action in cancer treatment","authors":"Marvellous Oyeyode , Mathew Tempel , Ted M. Lakowski , James R. Davie","doi":"10.1016/j.jbior.2025.101115","DOIUrl":"10.1016/j.jbior.2025.101115","url":null,"abstract":"<div><div>DNA-intercalating drugs (e.g., doxorubicin) have been used in cancer treatment since the 1960s. Multiple mechanisms have been observed with these drugs. These drugs intercalate into nucleosome-free regions of chromatin, which play a crucial role in regulating gene expression and genome organization. DNA intercalation by these drugs results in a plethora of events, including DNA damage, chromatin damage (histone eviction), erosion of chromatin organization, nucleolar condensation, RNA polymerase I and/or RNA polymerase II degradation, transcription arrest, deubiquitination of histone H2B ubiquitinated at lysine 120, topoisomerase I and/or II inhibition and/or trapping, and disruption of proteins associated with the elongating RNA polymerase II. These events may occur within hours following the addition of these drugs. At later times, changes to the DNA structure (e.g., the formation of Z DNA) occur, and eventually, the cells will die via apoptosis. This review will examine the mechanisms of action of DNA-intercalating drugs, specifically two anthracyclines (doxorubicin and aclarubicin) and a heteroaromatic compound (BMH-21). Doxorubicin and aclarubicin are used clinically to treat cancer, while BMH-21 remains in preclinical development. Reports on plasma pharmacokinetics of these anthracyclines will be tabulated, and the clinical relevance of the observed mechanisms of action for doxorubicin and aclarubicin will be assessed based on this information.</div></div>","PeriodicalId":7214,"journal":{"name":"Advances in biological regulation","volume":"98 ","pages":"Article 101115"},"PeriodicalIF":2.4,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145197774","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Continuous fractionated irradiation with irradiation-free intervals enhances survival and clonogenicity in osteosarcoma MG-63 cells via adaptive DNA damage response 通过适应性DNA损伤反应，以无照射间隔连续分次照射提高MG-63骨肉瘤细胞的存活率和克隆原性。

IF 2.4

Advances in biological regulation Pub Date : 2025-12-01 Epub Date: 2025-09-10 DOI: 10.1016/j.jbior.2025.101114

Hiroko Ikeda , Yuka Amano , Koki Hara , Yuito Tanaka , Eiki Isa , Nanami Shimomura , Toshifumi Tsujiuchi

{"title":"Continuous fractionated irradiation with irradiation-free intervals enhances survival and clonogenicity in osteosarcoma MG-63 cells via adaptive DNA damage response","authors":"Hiroko Ikeda , Yuka Amano , Koki Hara , Yuito Tanaka , Eiki Isa , Nanami Shimomura , Toshifumi Tsujiuchi","doi":"10.1016/j.jbior.2025.101114","DOIUrl":"10.1016/j.jbior.2025.101114","url":null,"abstract":"<div><div>Radiotherapy is a widely used treatment modality for various types of cancer. However, the adaptive resistance of tumor cells during radiotherapy poses a major challenge to therapeutic efficacy. This study aimed to evaluate whether continuous fractionated irradiation induces radioresistance in osteosarcoma MG-63 cells compared with single-dose exposure. To assess the effects of fractionated irradiation on cell survival, MG-63 cells were subjected to either single irradiation (SR; 0, 5, or 10 Gy) or continuous fractionated irradiation (5-CFR; 0, 1, or 2 Gy per day for five consecutive days), resulting in total doses of 0, 5, or 10 Gy, respectively. Compared with SR, 5-CFR significantly increased survival and promoted the formation of larger colonies, indicating enhanced clonogenicity. We further examined the effects of additional irradiation (AR) following 5-CFR and an irradiation-free interval. Cells pretreated with 5-CFR (0, 1, or 2 Gy) were subsequently exposed to a single dose of AR (2 Gy), resulting in total doses of 0, 7, or 12 Gy, respectively. MG-63 cells that received 5-CFR + AR exhibited significantly greater survival and increased colony size compared to those treated with SR + AR. To explore the cellular response to DNA damage following 5-CFR, we analyzed γ-H2AX and 53BP1 foci formation. Both markers increased in a dose-dependent manner after 5-CFR, suggesting effective recognition and repair of DNA double-strand breaks. Collectively, these results indicate that continuous fractionated irradiation with irradiation-free intervals confers greater radioresistance to MG-63 cells by enhancing survival and clonogenicity via an adaptive DNA damage response compared with SR.</div></div>","PeriodicalId":7214,"journal":{"name":"Advances in biological regulation","volume":"98 ","pages":"Article 101114"},"PeriodicalIF":2.4,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145079130","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0