{"title":"Commentary on: \"Structural insights into a bacterial β-glucosidase capable of degrading sesaminol triglucoside to produce sesaminol: toward the understanding of the aglycone recognition mechanism by the C-terminal lid domain\".","authors":"Masamichi Nagae","doi":"10.1093/jb/mvae094","DOIUrl":"https://doi.org/10.1093/jb/mvae094","url":null,"abstract":"<p><p>Sesaminol is an organic compound which shows the strong antioxidant, anti-inflammatory, and neuroprotective properties. Sesaminol triglucoside (STG) is glycosylated form of sesaminol and abundantly exists in sesame seeds. However, typical β-glucosidases could not deglycosylate STG probably due to its bulky aglycone. PSTG1 and 2 are β-glucosidases lately isolated from Paenibacillis sp. KB0459 and have the capacity to deglycosylate STG. A recent report by Yanai et al. (J. Biochem. 2023; 174:335-344) revealed that the unique domain architecture of PSTG1. Apart from other β-glucosdasies in GH3 family, PSTG1 has novel accessary domain (domain 4) at the C-terminus. Domain 4 contributes the dimer formation and is located close to the active site. Interestingly, several hydrophobic residues are exposed, suggesting that this domain may recognize the hydrophobic aglycone of STG. The physiological functions of the non-catalytic domains in glyco-enzymes are sometimes overlooked. This paper shed light on the aglycone recognition by novel accessary domain.</p>","PeriodicalId":15234,"journal":{"name":"Journal of biochemistry","volume":" ","pages":""},"PeriodicalIF":2.1,"publicationDate":"2025-01-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142921840","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 tumor relapse in intestinal cancer.","authors":"Taisuke Mizoo, Takeru Oka, Osamu Sugahara, Takafumi Minato, Tsunaki Higa, Keiichi I Nakayama","doi":"10.1093/jb/mvae082","DOIUrl":"https://doi.org/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 signaling and promotion of the epithelial-mesenchymal transition (EMT) in the cancer cells. Pharmacological inhibition of GPLD1 suppressed Wnt signaling 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 signaling and EMT-related cancer progression driven by CSCs.</p>","PeriodicalId":15234,"journal":{"name":"Journal of biochemistry","volume":" ","pages":""},"PeriodicalIF":2.1,"publicationDate":"2025-01-02","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":"Profiling translation in the nervous system.","authors":"Toshiharu Ichinose, Hiromu Tanimoto","doi":"10.1093/jb/mvae096","DOIUrl":"https://doi.org/10.1093/jb/mvae096","url":null,"abstract":"<p><p>Regulation at the level of translation is critical for functions in the nervous system, such as the formation of cell-type specific proteomes or plastic changes in neural circuits. While current knowledge of the translatome is relatively limited compared to transcriptome, a growing array of tools to analyze translation is becoming available. In this review, we introduce techniques for profiling translation on a genome-wide scale with a special emphasis on cell-type specific analyses in the nervous system. This includes polysome-profiling-seq, Translating Ribosome Affinity Purification (TRAP)-seq and ribosome profiling (Ribo-seq). We review recent advances to achieve spatial resolution of translatome analysis, such as genetic labeling of the targeted cells and cell sorting, and discuss the biological implications of translational regulation in the brain and potential future extensions.</p>","PeriodicalId":15234,"journal":{"name":"Journal of biochemistry","volume":" ","pages":""},"PeriodicalIF":2.1,"publicationDate":"2025-01-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142920566","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}
Masayoshi Suda, Tamar Tchkonia, James L Kirkland, Tohru Minamino
{"title":"Targeting senescent cells for the treatment of age-associated diseases.","authors":"Masayoshi Suda, Tamar Tchkonia, James L Kirkland, Tohru Minamino","doi":"10.1093/jb/mvae091","DOIUrl":"https://doi.org/10.1093/jb/mvae091","url":null,"abstract":"<p><p>Cellular senescence, which entails cellular dysfunction and inflammatory factor release-the senescence-associated secretory phenotype (SASP)-is a key contributor to multiple disorders, diseases, and the geriatric syndromes. Targeting senescent cells using senolytics has emerged as a promising therapeutic strategy for these conditions. Among senolytics, the combination of dasatinib and quercetin (D + Q) was the earliest and one of the most successful so far. D + Q delays, prevents, alleviates, or treats multiple senescence-associated diseases and disorders with improvements in healthspan across various preclinical models. While early senolytic therapies have demonstrated promise, ongoing research is crucial to refine them and address such challenges as off-target effects. Recent advances in senolytics include new drugs and therapies that target senescent cells more effectively. The identification of senescence-associated antigens-cell surface molecules on senescent cells-pointed to another promising means for developing novel therapies and identifying biomarkers of senescent cell abundance.</p>","PeriodicalId":15234,"journal":{"name":"Journal of biochemistry","volume":" ","pages":""},"PeriodicalIF":2.1,"publicationDate":"2024-12-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142894965","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}
Nittikarn Suwanawat, Takuya Ogawa, Yosuke Toyotake, Jun Kawamoto, Tatsuo Kurihara
{"title":"Biochemical characterization and mutational analysis of lysophosphatidic acid acyltransferases of Escherichia coli highlighting their involvement in the generation of membrane phospholipid diversity.","authors":"Nittikarn Suwanawat, Takuya Ogawa, Yosuke Toyotake, Jun Kawamoto, Tatsuo Kurihara","doi":"10.1093/jb/mvae093","DOIUrl":"https://doi.org/10.1093/jb/mvae093","url":null,"abstract":"<p><p>Lysophosphatidic acid acyltransferase (LPAAT) is an enzyme responsible for the second acylation step of phospholipid biosynthesis and transforms lysophosphatidic acid to phosphatidic acid, a universal precursor of various phospholipids. In addition to the well-studied plsC-encoded LPAAT (EcPlsC), we previously found that Escherichia coli has another LPAAT that is encoded by yihG (EcYihG). EcPlsC and EcYihG are integral membrane proteins and have never been solubilized and purified in their active form. To better understand the difference in their enzymatic functions and how the two paralogs differently contribute to lipid diversity, we established a method to purify both enzymes in their active form and comparatively analyzed their biochemical characteristics. Our findings illustrate that EcPlsC possesses the highest activity at pH 8.0 and 37 °C with selectivity for unsaturated fatty acyl-CoAs (e.g. palmitoleoyl-CoA), whereas EcYihG works optimally at pH 7.5 and 30 °C and prefers saturated fatty acyl-CoAs (e.g. myristoyl-CoA). In addition, we performed a mutational analysis based on AlphaFold2 models and revealed that one residue, which is located at the putative acyl-donor-selectivity tunnel entrance, plays a pivotal role in selecting acyl donor substrates. This provides new insights into how LPAATs recognize specific fatty acyl groups and incorporate them into membrane phospholipids.</p>","PeriodicalId":15234,"journal":{"name":"Journal of biochemistry","volume":" ","pages":""},"PeriodicalIF":2.1,"publicationDate":"2024-12-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142894961","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":"Etomoxir suppresses the expression of PPARgamma2 and inhibits the thermogenic gene induction of brown adipocytes through pathways other than β-oxidation inhibition.","authors":"Hiroki Shimura, Sota Yamamoto, Isshin Shiiba, Mami Oikawa, Shohei Uchinomiya, Akio Ojida, Shigeru Yanagi, Hisae Kadowaki, Hideki Nishitoh, Toshifumi Fukuda, Shun Nagashima, Tomoyuki Yamaguchi","doi":"10.1093/jb/mvae092","DOIUrl":"https://doi.org/10.1093/jb/mvae092","url":null,"abstract":"<p><p>Brown adipocytes are characterized by a high abundance of mitochondria, allowing them to consume fatty acids for heat production. Increasing the number of brown adipocytes is considered a promising strategy for combating obesity. However, the molecular mechanisms underlying their differentiation remain poorly understood. In this study, we demonstrate that etomoxir, an inhibitor of Carnitine Palmitoyltransferase 1 (CPT1), inhibits their differentiation through mechanisms independent of β-oxidation inhibition. In the presence of etomoxir during brown adipocyte differentiation, reduced expression of the thermogenic gene UCP1 and decreased lipid droplets formation were observed. Furthermore, a transient reduction in the expression of PPARγ2, a critical factor in adipocyte differentiation, was also observed in the presence of etomoxir. These findings suggest the presence of a regulatory mechanism that specifically enhances PPARγ2 expression during brown adipocyte differentiation, thereby modulating thermogenic gene expression.</p>","PeriodicalId":15234,"journal":{"name":"Journal of biochemistry","volume":" ","pages":""},"PeriodicalIF":2.1,"publicationDate":"2024-12-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142894963","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":"Interaction mapping between nucleoporins in the fission yeast Schizosaccharomyces pombe using mass-spectrometry.","authors":"Haruhiko Asakawa, Koji Nagao, Tatsuo Fukagawa, Chikashi Obuse, Yasushi Hiraoka, Tokuko Haraguchi","doi":"10.1093/jb/mvae095","DOIUrl":"https://doi.org/10.1093/jb/mvae095","url":null,"abstract":"<p><p>Nuclear pore complexes (NPCs) act as gateways across the nuclear envelope for molecular transport between the nucleus and the cytoplasm in eukaryotes. NPCs consist of several subcomplexes formed by multiple copies of approximately 30 different proteins known as nucleoporins (Nups). In the fission yeast Schizosaccharomyces pombe, the NPC structure is unique, particularly in its outer ring subcomplexes, where the cytoplasmic and nucleoplasmic outer rings are composed of distinct sets of proteins. However, it remains unclear how this unique outer ring structure in S. pombe is supported by interactions between subcomplexes or individual Nups. In this study, we investigated protein-protein interactions between S. pombe Nups using mass spectrometry and identified Nups that interact with each subcomplex or a specific Nup. The cytoplasmic outer ring Nups bind to both the cytoplasmic filament Nups and the inner ring Nups, while the nucleoplasmic outer ring Nups bind to the nuclear basket Nups in addition to the inner ring Nups. Among the inner ring Nups, Nup155 interacts with most of the cytoplasmic and nucleoplasmic outer ring Nups, suggesting that Nup155 may serve as a hub supporting the uniquely asymmetric outer ring structure of the S. pombe NPC.</p>","PeriodicalId":15234,"journal":{"name":"Journal of biochemistry","volume":" ","pages":""},"PeriodicalIF":2.1,"publicationDate":"2024-12-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142894964","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}
Sachie Chikamatsu, Yasufumi Sakakibara, Kimi Takei, Risa Nishijima, Koichi M Iijima, Michiko Sekiya
{"title":"Supplementation of essential amino acids suppresses age-associated sleep loss and sleep fragmentation but not loss of rhythm strength under yeast-restricted malnutrition in Drosophila.","authors":"Sachie Chikamatsu, Yasufumi Sakakibara, Kimi Takei, Risa Nishijima, Koichi M Iijima, Michiko Sekiya","doi":"10.1093/jb/mvae090","DOIUrl":"https://doi.org/10.1093/jb/mvae090","url":null,"abstract":"<p><p>Sleep quality and quantity decrease with age, and sleep disturbance increases the risk of many age-associated diseases. There is a significant relationship between nutritional status and sleep outcomes, with malnutrition inducing poor sleep quality in older adults. However, it remains elusive whether, and if so how, nutritional supplementation prevents age-associated sleep problems. Here, we utilized Drosophila to investigate the effects of a malnutrition diet with restricted yeast, a primary protein source, and supplementation of ten essential amino acids (EAAs) on sleep profiles during aging. Compared with the standard diet containing 2.7% yeast, the malnutrition diet containing 0.27% yeast significantly decreased target of rapamycin (TOR) signaling and shortened the lifespan of male Canton-S flies. By contrast, age-associated sleep loss, sleep fragmentation, and loss of rhythm strength were similarly observed under both diets. Supplementation of the malnutrition diet with EAAs in restricted yeast significantly ameliorated age-associated sleep loss and sleep fragmentation without altering loss of rhythm strength. It also rescued decreased TOR signaling activity but not the shortened lifespan, suggesting that the effects of EAAs on sleep integrity are independent of TOR activity and lifespan regulation. These results may help to develop dietary interventions that improve age-related sleep problems in humans.</p>","PeriodicalId":15234,"journal":{"name":"Journal of biochemistry","volume":" ","pages":""},"PeriodicalIF":2.1,"publicationDate":"2024-12-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142854214","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":"https://doi.org/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 widespread its use as a molecular switch in bionanomachines. calmodulin, 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 calmodulin target peptide M13 at the N-terminus of HRas exhibits reversible regulation of GTPase activity and the interaction between M13-HRas and the downstream signaling factor Raf by calcium ions with calmodulin. 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 analyzed 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 calmodulin.</p>","PeriodicalId":15234,"journal":{"name":"Journal of biochemistry","volume":" ","pages":""},"PeriodicalIF":2.1,"publicationDate":"2024-12-19","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}
Peter W T Lee, Minoru Kobayashi, Takakuni Dohkai, Itsuki Takahashi, Takumi Yoshida, Hiroshi Harada
{"title":"2-oxoglutarate-dependent Dioxygenases (2-OGDDs) as Oxygen Sensors: Their Importance in Health and Disease.","authors":"Peter W T Lee, Minoru Kobayashi, Takakuni Dohkai, Itsuki Takahashi, Takumi Yoshida, Hiroshi Harada","doi":"10.1093/jb/mvae087","DOIUrl":"https://doi.org/10.1093/jb/mvae087","url":null,"abstract":"<p><p>Since low oxygen conditions below physiological levels, hypoxia, is associated with various diseases, it is crucial to understand the molecular basis behind cellular response to hypoxia. Hypoxia-inducible factors (HIFs) have been revealed to primarily orchestrate the hypoxia response at the transcription level and have continuously attracted great attention over the past three decades. In addition to these hypoxia-responsive effector proteins, 2-oxoglutarate-dependent dioxygenase (2-OGDD) superfamily including prolyl-4-hydroxylase domain-containing proteins (PHDs) and factor inhibiting HIF-1 (FIH-1) have attracted even greater attention in recent years as factors that act as direct oxygen sensors due to their necessity of oxygen for the regulation of the expression and activity of the regulatory subunit of HIFs (HIF-α). Herein, we present a detailed classification of 2-OGDD superfamily proteins, such as Jumonji C-domain-containing histone demethylases (JmjC-KDMs), Ten-Eleven translocation (TET) enzymes, AlkB family of DNA/RNA demethylases, and Lysyl hydroxylases, and discusses their specific functions and associations with various diseases. By introducing the multifaceted roles of 2-OGDD superfamily proteins in the hypoxic response, this review aims to summarize the accumulated knowledge about the complex mechanisms governing cellular adaptation to hypoxia in various physiological and pathophysiological contexts.</p>","PeriodicalId":15234,"journal":{"name":"Journal of biochemistry","volume":" ","pages":""},"PeriodicalIF":2.1,"publicationDate":"2024-12-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142828707","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}