{"title":"Commentary for: a lipid scramblase TMEM41B is involved in the processing and transport of GPI-anchored proteins.","authors":"Hiroto Hirayama","doi":"10.1093/jb/mvae085","DOIUrl":"10.1093/jb/mvae085","url":null,"abstract":"<p><p>Glycosylphosphatidylinositol (GPI) anchoring is a conserved post-translational modification in eukaryotes. This modification allows acceptor proteins to be expressed at the cell surface as GPI-anchored proteins (GPI-APs), which play critical roles in various biological processes. It has been proposed that remodelling of GPI after transferring acceptor proteins, including the PGAP1-dependent deacylation of GPI-inositol, functions as a checkpoint for transporting mature GPI-APs from the endoplasmic reticulum (ER) to the Golgi. A previous study identified several factors involved in regulating PGAP1-dependent GPI-inositol deacylation, including proteins associated with the calnexin cycles, SELT and CLPTM1. A recent report by Cao et al., revealed that the loss of TMEM41B, an ER-resident lipid scramblase, rescues the defect in GPI-inositol deacylation in SELT-KO cells. Further investigation demonstrated that TMEM41B is essential for the efficient transport of both GPI-APs and transmembrane proteins from the ER to the Golgi. The study also found that PGAP1 proteins accumulate in the ER of TMEM41B-KO cells, suggesting that perturbations in the ER-membrane lipid integrity stabilize PGAP1 proteins, thereby enhancing the PGAP1 activity within the ER. These findings highlight that defects in TMEM41B impact two distinct processes: (i) the transport of GPI-APs from the ER to the Golgi, and (ii) the deacylation of GPI-APs.</p>","PeriodicalId":15234,"journal":{"name":"Journal of biochemistry","volume":" ","pages":"69-71"},"PeriodicalIF":2.1,"publicationDate":"2025-02-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142807016","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}
{"title":"Species-specific differences in acetaminophen hepatotoxicity depend on HSP70 expression level.","authors":"Daisuke Tsuji, Reiko Akagi","doi":"10.1093/jb/mvae086","DOIUrl":"10.1093/jb/mvae086","url":null,"abstract":"<p><p>Acetaminophen (N-Acetyl-p-aminophenol: APAP) is one of the most commonly used analgesic/antipyretic drugs with proven safety at therapeutic doses, however, over-dosage causes dose-dependent liver damage, leading to acute liver failure in severe cases. The level of APAP-induced liver injury has been known to vary amongst animal species, and APAP concentrations that induce cell death have been investigated using primary cultured cells. We constructed in vitro model of APAP-induced hepatotoxicity using mouse, rat and human hepatoma cell lines to investigate species differences in the APAP-induced cytotoxicity by monitoring cell death as a marker. The EC50 for each cell line was Hepa1-6 (mouse) < H-4-II-E (rat) < Hep3B (human), whilst the expression of heat shock protein 70 (HSP70), which was a typical molecular chaperone, positively correlated with the EC50 of each cell. Heat shock treatment, which caused activation of heat shock factor 1 (HSF1) followed by significant induction of HSP70, partially suppressed APAP-induced cell death in Hepa1-6 and H-4-II-E. Moreover, HSP70 or HSF1 siRNA treatment in Hep3B enhanced APAP-induced cell death. These results suggest that APAP-induced cell death in hepatoma cell lines may be partly mediated by protein denaturation and that the expression level of HSP70 has an inhibitory effect.</p>","PeriodicalId":15234,"journal":{"name":"Journal of biochemistry","volume":" ","pages":"133-139"},"PeriodicalIF":2.1,"publicationDate":"2025-02-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142828734","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}
{"title":"GPLD1+ cancer stem cells contribute to chemotherapy resistance and tumour relapse in intestinal cancer.","authors":"Taisuke Mizoo, Takeru Oka, Osamu Sugahara, Takafumi Minato, Tsunaki Higa, Keiichi I Nakayama","doi":"10.1093/jb/mvae082","DOIUrl":"10.1093/jb/mvae082","url":null,"abstract":"<p><p>Cancer stem cells (CSCs) play a central role in cancer progression, therapy resistance, and disease recurrence. With the use of a quadruple-mutant mouse intestinal cancer organoid model and single-cell RNA-sequencing analysis, we have now identified glycosylphosphatidylinositol-specific phospholipase D1 (GPLD1), an enzyme that catalyzes the cleavage of glycosylphosphatidylinositol (GPI) anchors of membrane proteins, as a marker of slowly cycling CSCs. Ablation of Gpld1+ cells in combination with 5-fluorouracil treatment greatly attenuated cell viability in and regrowth of the intestinal cancer organoids. In addition, we identified serine protease 8 (PRSS8) as a key substrate of GPLD1 in human colorectal cancer cells. GPLD1 cleaves the GPI anchor of PRSS8 and thereby mediates release of the protease from the plasma membrane, resulting in the activation of Wnt signalling and promotion of the epithelial-mesenchymal transition (EMT) in the cancer cells. Pharmacological inhibition of GPLD1 suppressed Wnt signalling activity and EMT in association with upregulation of the amount of functional PRSS8 at the plasma membrane. Our findings suggest that targeting of GPLD1 in colorectal cancer might contribute to a new therapeutic strategy that is based on suppression of Wnt signalling and EMT-related cancer progression driven by CSCs.</p>","PeriodicalId":15234,"journal":{"name":"Journal of biochemistry","volume":" ","pages":"105-119"},"PeriodicalIF":2.1,"publicationDate":"2025-02-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142914950","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}
{"title":"Ionic control of small GTPase HRas using calmodulin.","authors":"Yassine Sabek, Ziyun Zhang, Nobuyuki Nishibe, Shinsaku Maruta","doi":"10.1093/jb/mvae089","DOIUrl":"10.1093/jb/mvae089","url":null,"abstract":"<p><p>HRas is a small GTPase that plays physiologically important roles in various intracellular signal transduction processes, such as cell growth and proliferation. The structure and action mechanisms of HRas have been well characterized, leading to its widespread use as a molecular switch in bionanomachines. Calmodulin (CaM), a calcium ion-binding protein, acts as an ion-binding molecular switch and activates the target enzymes. We previously demonstrated that the fusion protein of HRas (M13-HRas) with the CaM target peptide M13 at the N-terminus of HRas exhibits reversible regulation of GTPase activity and the interaction between M13-HRas and the downstream signalling factor Raf by calcium ions with CaM. In this study, we prepared two new HRas fusion proteins with the M13 peptide at the C-terminus (HRas-M13) and both termini (M13-HRas-M13) of HRas and analysed the calcium-dependent regulation of HRas function. M13-HRas-M13 more efficiently controlled GTPase, interaction with Raf and the HRas regulator GEF by calcium ions with CaM.</p>","PeriodicalId":15234,"journal":{"name":"Journal of biochemistry","volume":" ","pages":"153-161"},"PeriodicalIF":2.1,"publicationDate":"2025-02-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142854209","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}
{"title":"Two-sided function of osteopontin during osteoblast differentiation.","authors":"Fredy Mardiyantoro, Norika Chiba, Chang-Hwan Seong, Ryohei Tada, Tomokazu Ohnishi, Norifumi Nakamura, Tetsuya Matsuguchi","doi":"10.1093/jb/mvae080","DOIUrl":"10.1093/jb/mvae080","url":null,"abstract":"<p><p>Osteopontin (OPN) is expressed in various cell types including osteoblasts. OPN expression level is robustly increased during osteoblast differentiation. Although OPN was initially found as a secretory protein (sOPN), recent reports identified the intracellular isoform of OPN (iOPN). Distinct functions of each OPN isoform in osteoblasts, however, are not well established. Here, using the Tet-On inducible expression system, we examined the role of each OPN isoform during osteoblast differentiation. Induced overexpression of wild type OPN (wtOPN), which includes both sOPN and iOPN, significantly increased matrix mineralization and osteogenic marker gene expression during osteogenic differentiation induced by either ascorbic acid or bone morphogenetic protein (BMP) 9. In contrast, these osteogenic differentiation processes were significantly inhibited by the specific overexpression of iOPN. Furthermore, the addition of recombinant OPN or neutralizing anti-OPN antibody to the culture medium exerted promotive or inhibitory effect on osteoblast differentiation, respectively. These data strongly indicate that iOPN exerts inhibitory effects on osteoblast differentiation, whereas sOPN exerts positive effects. We also found that the secretion process of OPN is positively regulated by c-Jun N-terminal kinase (JNK) activity in osteoblasts.</p>","PeriodicalId":15234,"journal":{"name":"Journal of biochemistry","volume":" ","pages":"121-131"},"PeriodicalIF":2.1,"publicationDate":"2025-02-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142807033","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}
{"title":"RMST: a long noncoding RNA involved in cancer and disease.","authors":"Hidenori Tani","doi":"10.1093/jb/mvae083","DOIUrl":"10.1093/jb/mvae083","url":null,"abstract":"<p><p>Long non-coding RNA rhabdomyosarcoma 2-associated transcript (RMST) is a crucial regulator in various biological processes, particularly in neurogenesis and cancer progression. This review summarizes current knowledge on structure, expression patterns and functional roles across different organs and diseases of RMST. RMST exhibits tissue-specific expression, notably in brain tissues and vascular endothelial cells, and plays a significant role in neuronal differentiation through interaction with SRY-box 2. In cancer, RMST predominantly functions as a tumour suppressor, with context-dependent roles observed across different cancer types. RMST is also implicated in neurological disorders, cardiovascular diseases and Hirschsprung's disease. Mechanistically, RMST acts as a competing endogenous RNA and a transcriptional regulator, interacting with various microRNAs and proteins to modulate gene expression. The potential of RMST as a biomarker and therapeutic target is increasingly recognized, particularly in atherosclerosis and cancer. While current findings are promising, further research is needed to fully elucidate the functions and translate these insights into clinical applications of RMST. This review underscores the significance of RMST in cellular processes and disease pathogenesis, highlighting its potential as a novel target for diagnostic and therapeutic interventions.</p>","PeriodicalId":15234,"journal":{"name":"Journal of biochemistry","volume":" ","pages":"73-78"},"PeriodicalIF":2.1,"publicationDate":"2025-02-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142824155","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}
{"title":"Maintenance of the Golgi ribbon structure by the KASH protein Jaw1.","authors":"Morihisa Fujita","doi":"10.1093/jb/mvae081","DOIUrl":"10.1093/jb/mvae081","url":null,"abstract":"<p><p>The Golgi apparatus is an organelle responsible for modification, secretion and transport of biomolecules. Its structure and morphology are crucial for the efficient processing and proper transport of proteins. The maintenance of this Golgi ribbon structure involves multiple proteins including GRASP and golgin proteins and the microtubule network. Particularly, the microtubule network extending from the Golgi is important for the Golgi ribbon formation and positioning. A recent report by Okumura et al. (J. Biochem. 2023; 173: 383-392) demonstrated that Jaw1, one of the Klarsicht/ANC-1/Syne/homology (KASH) proteins that are components of the linker of nucleoskeleton and cytoskeleton (LINC) complex, is essential for maintaining the Golgi ribbon structure. Knockdown of Jaw1 disrupted the Golgi ribbon structure leading to the fragmentation, whilst the Golgi ministacks were preserved. Acetylated tubulin, a marker of the Golgi-derived microtubule network, became more dispersed, losing its local compactness in the Jaw-depleted cells. These phenomena suggest that Jaw1 is required to maintain the proper organization of the Golgi-derived microtubule network.</p>","PeriodicalId":15234,"journal":{"name":"Journal of biochemistry","volume":" ","pages":"65-67"},"PeriodicalIF":2.1,"publicationDate":"2025-02-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142668113","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}
{"title":"Exploring the roles of Lem2 and Bqt4 in lipid metabolism for nuclear envelope maintenance: a novel perspective.","authors":"Kei-Ichiro Ishiguro","doi":"10.1093/jb/mvae072","DOIUrl":"10.1093/jb/mvae072","url":null,"abstract":"<p><p>The nuclear envelope (NE) is a double-membrane structure critical for genome maintenance and cellular function, composed of the inner and outer nuclear membranes. In fission yeast, the inner nuclear membrane (INM) proteins Lem2 and Bqt4 are essential for maintaining NE integrity. The study published by Hiraoka group explores the interactions between Lem2 and Bqt4 with lipid synthesis enzymes, addressing their roles in NE maintenance. The authors identified Lem2- and Bqt4-binding proteins using immunoprecipitation and mass spectrometry, revealing that Lem2 interacts with lipid synthesis enzymes, whilst Bqt4 binds to an enzyme that involves in glucosylceramide synthesis. These findings suggest that Lem2 and Bqt4 independently contribute to NE structure and its integrity through distinct lipid metabolic pathways, highlighting their complementary roles in nuclear membrane homeostasis. This study represents a significant step forward in the field of NE biology to unravel the complexities of nuclear membrane dynamics.</p>","PeriodicalId":15234,"journal":{"name":"Journal of biochemistry","volume":" ","pages":"1-3"},"PeriodicalIF":2.1,"publicationDate":"2025-01-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142501136","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}
{"title":"Open and closed structures of L-arginine oxidase by cryo-electron microscopy and X-ray crystallography.","authors":"Hiroki Yamaguchi, Kazutoshi Takahashi, Nobutaka Numoto, Hiroshi Suzuki, Moemi Tatsumi, Akiko Kamegawa, Kouki Nishikawa, Yasuhisa Asano, Toshimi Mizukoshi, Hiroshi Miyano, Yoshinori Fujiyoshi, Masayuki Sugiki","doi":"10.1093/jb/mvae070","DOIUrl":"10.1093/jb/mvae070","url":null,"abstract":"<p><p>L-arginine oxidase (AROD, EC 1.4.3.25) is an oxidoreductase that catalyses the deamination of L-arginine, with flavin adenine dinucleotide (FAD) as a cofactor. Recently identified AROD from Pseudomonas sp. TPU 7192 (PT-AROD) demonstrates high selectivity for L-arginine. This enzyme is useful for accurate assays of L-arginine in biological samples. The structural characteristics of the FAD-dependent AROD, however, remain unknown. Here, we report the structure of PT-AROD at a resolution of 2.3 Å by cryo-electron microscopy. PT-AROD adopts an octameric structure with D4 symmetry, which is consistent with its molecular weight in solution, estimated by mass photometry. Comparative analysis of this structure with that determined using X-ray crystallography reveals open and closed forms of the lid-like loop at the entrance to the substrate pocket. Furthermore, mutation of Glu493, located at the substrate binding site, diminishes substrate selectivity, suggesting that this residue contributes significantly to the high selectivity of PT-AROD.</p>","PeriodicalId":15234,"journal":{"name":"Journal of biochemistry","volume":" ","pages":"27-36"},"PeriodicalIF":2.1,"publicationDate":"2025-01-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11694665/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142466392","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}
{"title":"Absolute quantification of BACH1 and BACH2 transcription factors in B and plasma cells reveals their dynamic changes and unique roles.","authors":"Takeshi Kurasawa, Akihiko Muto, Mitsuyo Matsumoto, Kyoko Ochiai, Kazutaka Murayama, Kazuhiko Igarashi","doi":"10.1093/jb/mvae065","DOIUrl":"10.1093/jb/mvae065","url":null,"abstract":"<p><p>Changes in the absolute protein amounts of transcription factors are important for regulating gene expression during cell differentiation and in responses to changes in the cellular and extracellular environment. However, few studies have focused on the absolute quantification of mammalian transcription factors. In this study, we established an absolute quantification method for the transcription factors BACH1 and BACH2, which are expressed in B cells and regulated by direct heme binding. The method used purified recombinant proteins as controls in western blotting and was applied to mouse naïve B cells in the spleen, as well as activated B cells and plasma cells. BACH1 was present in naïve B cells at approximately half the levels of BACH2. In activated B cells, BACH1 decreased compared to naïve B cells, whilst BACH2 increased. In plasma cells, BACH1 increased back to the same extent as in naïve B cells, whilst BACH2 was not detected. Their target genes, Prdm1 and Hmox1, were highly induced in plasma cells. BACH1 was found to undergo degradation with lower concentrations of heme than BACH2. Therefore, BACH1 and BACH2 are similarly abundant in B cells but differ in heme sensitivity, potentially regulating gene expression differently depending on their heme responsiveness.</p>","PeriodicalId":15234,"journal":{"name":"Journal of biochemistry","volume":" ","pages":"449-459"},"PeriodicalIF":2.1,"publicationDate":"2024-12-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142347461","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}