Journal of biochemistry最新文献

FRET-based biosensor moxCRONOS enables quantitative monitoring of macromolecular crowding in organelles and protein aggregates. 基于fret的生物传感器moxCRONOS能够定量监测细胞器和蛋白质聚集体中的大分子拥挤。

IF 1.7 4区生物学

Journal of biochemistry Pub Date : 2025-09-30 DOI: 10.1093/jb/mvaf056

Yurina Nakajima, Hiroaki Suzuki, Tamami Miyagi, Kohsuke Kanekura

{"title":"FRET-based biosensor moxCRONOS enables quantitative monitoring of macromolecular crowding in organelles and protein aggregates.","authors":"Yurina Nakajima, Hiroaki Suzuki, Tamami Miyagi, Kohsuke Kanekura","doi":"10.1093/jb/mvaf056","DOIUrl":"https://doi.org/10.1093/jb/mvaf056","url":null,"abstract":"Macromolecular crowding is a fundamental property of the intracellular environment that influences protein folding, enzymatic activity, and phase behavior. Disruptions to the homeostasis of macromolecular crowding can drive pathological processes, such as aberrant liquid-liquid phase separation and protein aggregation, which are central features of several neurodegenerative diseases. However, tools for quantifying crowding and aggregation remain limited. Here, we describe moxCRONOS, a Förster resonance energy transfer (FRET)-based biosensor that enables the quantitative measurement of macromolecular crowding and protein condensation. moxCRONOS retains the optical properties of the original CRONOS sensor but offers enhanced stability in oxidative environments, such as within the endoplasmic reticulum or under sodium arsenite treatment, allowing for direct comparison of crowding levels across organelles regardless of redox conditions. Moreover, when fused to dipeptide repeat proteins associated with C9ORF72-linked neurodegeneration, moxCRONOS detects aggregation-prone states-especially in cells expressing glycine-alanine (GA) repeats. Using fluorescence-activated cell sorting, we achieved sensitive and quantitative detection of heterogeneous high-FRET cell populations containing GA aggregates. FRET signal intensity increased upon treatment with a molecular crowding agent or a proteasome inhibitor. These findings establish moxCRONOS as a versatile biosensor for investigating both physiological macromolecular crowding and pathological protein aggregation, with significant potential for disease modeling and therapeutic screening.","PeriodicalId":15234,"journal":{"name":"Journal of biochemistry","volume":" ","pages":""},"PeriodicalIF":1.7,"publicationDate":"2025-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145199608","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

Comprehensive identification of proteins interacting with long non-coding RNA TUG1 in R-loop regulation. R-Loop调控中与长链非编码RNA TUG1相互作用蛋白的综合鉴定

IF 1.7 4区生物学

Journal of biochemistry Pub Date : 2025-09-30 DOI: 10.1093/jb/mvaf042

Jingqi Xie, Miho M Suzuki, Kenta Iijima, Keiko Shinjo, Tatsunori Nishimura, Shinya Watanabe, Reiko Nakagawa, Tatsuo Ito, Yutaka Kondo

{"title":"Comprehensive identification of proteins interacting with long non-coding RNA TUG1 in R-loop regulation.","authors":"Jingqi Xie, Miho M Suzuki, Kenta Iijima, Keiko Shinjo, Tatsunori Nishimura, Shinya Watanabe, Reiko Nakagawa, Tatsuo Ito, Yutaka Kondo","doi":"10.1093/jb/mvaf042","DOIUrl":"10.1093/jb/mvaf042","url":null,"abstract":"Long non-coding RNAs (lncRNAs) regulate a wide array of cellular processes through interactions with RNA-binding proteins (RBPs). Taurine Upregulated Gene 1 (TUG1) is an lncRNA that is overexpressed in many types of cancer and has been implicated in resolving R-loops, thereby maintaining genomic integrity. However, the full spectrum of its protein interactions and stress-responsive dynamics remains unclear. Here, we employed CRISPR-assisted RNA-protein interaction detection (CARPID) combined with mass spectrometry to comprehensively identify the interacting proteins of TUG1 in HEK293T cells. Using three distinct single-guide RNAs (sgRNAs) targeting different regions of TUG1, we consistently identified 17 TUG1-interacting proteins under basal conditions. Upon camptothecin (CPT) treatment, which induces R-loop formation, the number of associated proteins increased to 25. Under these stress conditions, the protein sets identified by each sgRNA showed greater overlap, suggesting a more conserved pattern of TUG1-protein interactions in response to R-loop accumulation. Many of these proteins are known R-loop-associated factors, including DEAD/DEAH-box RNA helicases, poly(ADP-ribose) polymerase 1 (PARP1) and heterogeneous nuclear ribonucleoproteins (HNRNPs), indicating that TUG1 engages R-loop regulatory machinery to maintain genome integrity. Our study provides new insights into lncRNA-mediated R-loop regulation and its role in genome maintenance.","PeriodicalId":15234,"journal":{"name":"Journal of biochemistry","volume":" ","pages":"251-265"},"PeriodicalIF":1.7,"publicationDate":"2025-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12480733/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144626414","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

Interaction between a fluoroquinolone derivative KG022 and RNAs: effect of the bulged residues. 氟喹诺酮衍生物KG022与rna的相互作用：凸起残基的作用。

IF 1.7 4区生物学

Journal of biochemistry Pub Date : 2025-09-30 DOI: 10.1093/jb/mvaf039

Rika Ichijo, Gota Kawai

引用次数: 0

Repressive S-adenosylmethionine biosynthesis status inhibits transcription of HeT-A retrotransposon in the germline of Drosophila. 抑制s -腺苷蛋氨酸生物合成状态抑制果蝇种系HeT-A反转录转座子的转录。

IF 1.7 4区生物学

Journal of biochemistry Pub Date : 2025-09-30 DOI: 10.1093/jb/mvaf041

Yoshiki Hayashi, Shinjiro Hino, Tetsuya Sato, Soshiro Kashio, Kiito Otsubo, Kuniaki Saito, Ban Sato, Natsuko Kawano, Daisuke Saito, Masayuki Miura, Mikita Suyama, Mitsuyoshi Nakao, Satoru Kobayashi

{"title":"Repressive S-adenosylmethionine biosynthesis status inhibits transcription of HeT-A retrotransposon in the germline of Drosophila.","authors":"Yoshiki Hayashi, Shinjiro Hino, Tetsuya Sato, Soshiro Kashio, Kiito Otsubo, Kuniaki Saito, Ban Sato, Natsuko Kawano, Daisuke Saito, Masayuki Miura, Mikita Suyama, Mitsuyoshi Nakao, Satoru Kobayashi","doi":"10.1093/jb/mvaf041","DOIUrl":"10.1093/jb/mvaf041","url":null,"abstract":"S-adenosylmethionine (SAM) is the major cellular methyl donor and regulates gene expression through epigenetic and other methylation-related processes. While SAM biosynthesis influences a variety of biological phenomena including ageing and disease, its cell type-specific regulation and functional implications remain poorly understood. In this study, we report that the Drosophila germline exhibits a uniquely repressive SAM biosynthesis status during gametogenesis, as indicated by low expression of SAM synthetase (Sam-S), a key enzyme for SAM production. Experimentally enhancing SAM biosynthesis in the germline led to increased expression of retrotransposons, with HeT-A, a telomere-specific element, showing the most pronounced response. We also observed increased promoter activity of HeT-A under high SAM conditions, along with accumulation of N6-methyladenine (6 mA), the major form of DNA methylation in the Drosophila genome. Although a direct causal link between 6 mA levels and transcription was not broadly observed across other retrotransposons or genes, these results raise the possibility that SAM levels modulate HeT-A expression at least in part through DNA methylation. Our findings highlight a previously underexplored metabolic feature of the Drosophila germline and suggest that SAM availability contributes to the regulation of retrotransposon activity in a lineage-specific manner.","PeriodicalId":15234,"journal":{"name":"Journal of biochemistry","volume":" ","pages":"217-228"},"PeriodicalIF":1.7,"publicationDate":"2025-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144540355","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 tumor promoter 12-O-tetradecanoylphorbol-13-acetate suppresses cell proliferation in metastatic melanoma through TC-PTP/PTPN2 and SH-PTP2/PTPN11. 肿瘤启动子12- o - tetradecanoylphorol -13-acetate通过TC-PTP/PTPN2和SH-PTP2/PTPN11抑制转移性黑色素瘤细胞增殖。

IF 1.7 4区生物学

Journal of biochemistry Pub Date : 2025-09-30 DOI: 10.1093/jb/mvaf040

Yuki Akamatsu, Mami Onishi, Taiki Nagano, Masahiro Oka, Shinji Kamada, Tetsushi Iwasaki

{"title":"The tumor promoter 12-O-tetradecanoylphorbol-13-acetate suppresses cell proliferation in metastatic melanoma through TC-PTP/PTPN2 and SH-PTP2/PTPN11.","authors":"Yuki Akamatsu, Mami Onishi, Taiki Nagano, Masahiro Oka, Shinji Kamada, Tetsushi Iwasaki","doi":"10.1093/jb/mvaf040","DOIUrl":"10.1093/jb/mvaf040","url":null,"abstract":"Despite being a carcinogen, the phorbol ester 12-O-tetradecanoylphorbol-13-acetate (TPA) inhibits metastatic melanoma growth by downregulating the signal transducer and activator of transcription 3. However, the molecular mechanisms remain unclear. The aim of this study was to identify tyrosine phosphatases that are involved in TPA-induced inhibition of cell proliferation in metastatic melanoma cells. We screened protein tyrosine phosphatases (PTPs) required for TPA-mediated inhibition of cell proliferation. We identified two PTPs, SH2 domain-containing PTP2 (SH-PTP2/PTPN11) and T-cell PTP (TC-PTP/PTPN2) that play key roles in TPA-mediated inhibition of metastatic melanoma cell growth. Transient expression of SH-PTP2 and TC-PTP induced G0/G1 cell cycle arrest in a phosphatase-dependent manner. Furthermore, SH-PTP2 was translocated to the cell membrane upon TPA treatment, resulting in a decrease in Janus kinase 2 activity. TC-PTP is localized in the nucleus together with the adapter protein ubiquitin-like protein 4A; TC-PTP was translocated to the nuclear periphery upon TPA stimulation. These two signaling pathways, involving SH-PTP2 and TC-PTP, are distinct from those observed in normal melanocytes and benign melanoma cells. These pathways represent previously unknown responses to TPA specific to metastatic melanoma cells. Overall, these findings may contribute to the development of new anticancer agents.","PeriodicalId":15234,"journal":{"name":"Journal of biochemistry","volume":" ","pages":"237-250"},"PeriodicalIF":1.7,"publicationDate":"2025-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144528140","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

UNC5B is an isoform-dependent target for ectodomain shedding. UNC5B是胞外结构域脱落的同工异构体依赖性靶标。

IF 1.7 4区生物学

Journal of biochemistry Pub Date : 2025-09-30 DOI: 10.1093/jb/mvaf043

Kotaro Sugimoto, Eichi Watabe, Mio Takuma, Kaname Nagahara, Toshinori Sawano, Mihoko Kajita, Junichi Takagi, Hidehito Kuroyanagi, Kyoko Shirakabe

引用次数: 0

A novel O-GlcNAcylation at threonine 71 of histone H4 is a component of heterochromatin. 组蛋白H4苏氨酸71的o - glcn酰化是异染色质的一个组成部分。

IF 1.7 4区生物学

Journal of biochemistry Pub Date : 2025-09-30 DOI: 10.1093/jb/mvaf044

Koji Hayakawa, Mitsuko Hirosawa, Daisuke Nara, Nobuyuki Fujiwara, Kunio Shiota, Satoshi Tanaka

{"title":"A novel O-GlcNAcylation at threonine 71 of histone H4 is a component of heterochromatin.","authors":"Koji Hayakawa, Mitsuko Hirosawa, Daisuke Nara, Nobuyuki Fujiwara, Kunio Shiota, Satoshi Tanaka","doi":"10.1093/jb/mvaf044","DOIUrl":"10.1093/jb/mvaf044","url":null,"abstract":"Previous studies have reported several O-linked N-acetylglucosamine (O-GlcNAc) modifications of core histones H2A, H2B, H3 and H4. In parallel, the characteristics and functions of O-GlcNAcylated histones are also shown, and they are involved in various cellular processes, such as development and tumorigenesis, indicating that the exploration of new histone O-GlcNAcylation contributes significantly to the elucidation of molecular mechanisms occurring in cells. Here, we report that O-GlcNAcylation occurs at threonine 71 of histone H4 (H4T71Gc) by developing a monoclonal antibody that recognizes the O-GlcNAcylated H4T71 peptide. Threonine 71 of histone H4 is highly conserved from metazoans to mammals, and H4T71Gc can be detected. Chromatin immunoprecipitation-seq and biochemical analysis revealed that H4T71Gc was localized to the region where histone H3 modified by trimethylation of lysine 9 (H3K9me3) was enriched in a genome-wide manner. H3K9me3 is known to function in chromatin condensation, suggesting that H4T71Gc plays a role in both the progression and maintenance of condensed chromatin in several species.","PeriodicalId":15234,"journal":{"name":"Journal of biochemistry","volume":" ","pages":"277-285"},"PeriodicalIF":1.7,"publicationDate":"2025-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144846635","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

Nucling, a stress-inducible protein associated with apoptosomes, is important for microglial polarization/activation in the brain neuroinflamation. 成核是一种与凋亡相关的应激诱导蛋白，对脑神经炎症中的小胶质细胞极化/激活很重要。

IF 1.7 4区生物学

Journal of biochemistry Pub Date : 2025-09-10 DOI: 10.1093/jb/mvaf055

Tuan Anh Pham, Takashi Sakai, Huy Van Dang, Diem Hong Tran, Yuji Shishido, Nam Hoang Tran, Kiyoshi Fukui

{"title":"Nucling, a stress-inducible protein associated with apoptosomes, is important for microglial polarization/activation in the brain neuroinflamation.","authors":"Tuan Anh Pham, Takashi Sakai, Huy Van Dang, Diem Hong Tran, Yuji Shishido, Nam Hoang Tran, Kiyoshi Fukui","doi":"10.1093/jb/mvaf055","DOIUrl":"https://doi.org/10.1093/jb/mvaf055","url":null,"abstract":"Microglia, the central nervous system's resident macrophages, are critical for immune defense, protecting neurons during infection. Their role in postnatal brain development, particularly after injury, remains unclear. Nucling, a protein up-regulated during cardiac muscle differentiation, regulates NF-κB, influencing apoptosis and cell proliferation. In this study, we examined the role of Nucling in microglial activation using wild-type (WT) and Nucling-knockout (KO) neonatal mice subjected to poly(I:C), a viral mimic. Poly(I:C) treatment increased Iba1-positive microglia in both genotypes; however, KO mice showed a significantly exaggerated response in both cortical and hippocampal regions. Furthermore, while pro-inflammatory M1 markers (iNOS, CD86, TNFα, IL-6) were upregulated in both WT and KO mice, the anti-inflammatory M2 marker Arginase 1 (Arg1) was induced in WT but significantly suppressed in KO mice, indicating impaired M2 polarization. These findings suggest Nucling is essential for maintaining microglial polarization, supporting immunological processes against pathogens, and aiding central nervous system development.","PeriodicalId":15234,"journal":{"name":"Journal of biochemistry","volume":" ","pages":""},"PeriodicalIF":1.7,"publicationDate":"2025-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145029949","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

Transcription and translation efficiency is reduced in cholesterol-containing liposomes. 在含胆固醇的脂质体中，转录和翻译效率降低。

IF 1.7 4区生物学

Journal of biochemistry Pub Date : 2025-09-03 DOI: 10.1093/jb/mvaf032

Shota Fukuoka, Ayu Shimomura, Yuya Katsumura, Masaya Oki, Gakushi Tsuji

引用次数: 0

Transcriptional control of brown adipocyte differentiation and function by NFIA: recent perspectives on deciphering metabolic diseases. NFIA对棕色脂肪细胞分化和功能的转录控制：解读代谢疾病的最新观点。

IF 1.7 4区生物学

Journal of biochemistry Pub Date : 2025-09-03 DOI: 10.1093/jb/mvaf038

Yuta Hiraike

引用次数: 0