{"title":"Identification and characterization of a novel haemolytic and haemagglutinating bifunctional lectin from the coral Acropora millepora.","authors":"Yuki Takahashi, Ryosuke Kamimura, Ryo Toyama, Shun Kita, Yuki Ushijima, Shigeto Taniyama, Hideaki Unno, Tomomitsu Hatakeyama, Shuichiro Goda","doi":"10.1093/jb/mvaf010","DOIUrl":"10.1093/jb/mvaf010","url":null,"abstract":"<p><p>Two genes, AML-I and AML-II, have been reported to exhibit increased expression during the development of the coral Acropora millepora. They show amino acid sequence homology with CEL-III, a haemolytic lectin found in the sea cucumber Cucumaria echinata. CEL-III binds to carbohydrate chains on the surface of erythrocytes, forming heptameric pores in their membranes. To clarify the role of these proteins in coral, we identified and elucidated their functions. The carbohydrate-binding domains of them showed similar carbohydrate-binding specificity as that of CEL-III. AML-I showed haemagglutinating activity in erythrocytes, whereas AML-II can only be prepared as an aggregate and its function could not yet be determined. AML-IΔC and AML-IIΔC mutants were generated through deletion of the C-terminal extended amino acid residues of them relative to CEL-III. AML-IΔC showed haemolytic activity towards erythrocytes, whereas AML-IIΔC showed no activity. A tobacco etch virus (TEV) protease recognition site was inserted into the C-terminus of AML-I to regulate these activities. The haemagglutinating activity of AML-I was converted into haemolytic activity after TEV protease treatment. As a result, TEV protease could control the haemolytic and haemagglutinating activity of the lectin, which could be useful as an anticancer or antiviral drug because of its cytotoxic activity.</p>","PeriodicalId":15234,"journal":{"name":"Journal of biochemistry","volume":" ","pages":"375-386"},"PeriodicalIF":2.1,"publicationDate":"2025-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143449134","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":"CDC42 missense mutations and human diseases: from neurodevelopmental disorders to autoinflammation.","authors":"Takahiro Yasumi","doi":"10.1093/jb/mvaf021","DOIUrl":"https://doi.org/10.1093/jb/mvaf021","url":null,"abstract":"<p><p>Cdc42 is a member of the Rho family of small GTPases that controls various cellular responses by interacting with more than 45 effector proteins. Recent advances in genomic analysis reveal that Cdc42 missense variants cause various pathological phenotypes, including severe autoinflammation, suggesting previously unknown involvement of Cdc42 in innate immunity. This review aims to update our understanding of how CDC42 mutations are involved in human diseases, with emphasis on early-onset autoinflammation associated with mutations located at the carboxyl-terminus. Further analysis is required to elucidate the complex inflammatory mechanisms induced by various Cdc42 variants, leading to development of therapies that inhibit inflammatory pathologies.</p>","PeriodicalId":15234,"journal":{"name":"Journal of biochemistry","volume":" ","pages":""},"PeriodicalIF":2.1,"publicationDate":"2025-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144036536","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":"High GRWD1 expression may predict clinically aggressive lower grade glioma, skin cutaneous melanoma, and kidney renal clear cell carcinoma carrying wild-type p53: a systematic study based on TCGA data analysis.","authors":"Kota Kayama, Akihiro Ooga, Kouji Hasetsu, Ryoma Kokubo, Nozomi Sugimoto, Masatoshi Fujita","doi":"10.1093/jb/mvaf004","DOIUrl":"10.1093/jb/mvaf004","url":null,"abstract":"<p><p>Glutamate-rich WD40 repeat-containing 1 (GRWD1) is a novel oncogene/oncoprotein that downregulates the p53 tumour suppressor protein through several mechanisms. One important mechanism involves binding of GRWD1 to RPL11, which competitively inhibits the RPL11-MDM2 interaction and releases RPL11-mediated suppression of MDM2 ubiquitin ligase activity towards p53. Here, we mined the TCGA (The Cancer Genome Atlas) database to gain in-depth insight into the clinical relevance of GRWD1. We found that high expression of GRWD1 is associated with a poor prognosis for lower grade glioma (LGG) of the brain, skin cutaneous melanoma (SKCM), and kidney renal clear cell carcinoma (KIRC) carrying wild-type p53. Further investigations revealed that copy number alterations in the GRWD1 gene are one determinant of GRWD1 expression level. By contrast, even in patients with a diploid GRWD1 gene, high GRWD1 expression was associated with a poor prognosis for LGG, SKCM, and KIRC carrying wild-type p53. Additional studies suggest that some transcriptional factors may be involved in regulation of GRWD1 in cancers with a diploid GRWD1 gene. Taken together, the data presented herein suggest that high expression of GRWD1 may contribute to malignant behaviour, and predict a clinically unfavourable prognosis for LGG, SKCM, and KIRC carrying wild-type p53.</p>","PeriodicalId":15234,"journal":{"name":"Journal of biochemistry","volume":" ","pages":"351-361"},"PeriodicalIF":2.1,"publicationDate":"2025-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142983613","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":"Photocontrol of the small GTPase Ras using its regulatory factor, GTPase-activating protein, modified with photochromic nanodevices.","authors":"Rajib Ahmed, Nobuyuki Nishibe, Ziyun Zhang, Shinsaku Maruta","doi":"10.1093/jb/mvaf009","DOIUrl":"10.1093/jb/mvaf009","url":null,"abstract":"<p><p>Ras, a small GTPase, is central to the regulation of diverse cellular processes including transcription, cell cycle progression, growth, migration, cytoskeletal reorganization, apoptosis, cell survival and senescence. Ras activation is mediated by GTP binding, whereas its inactivation occurs via GDP binding, which is tightly controlled by guanine nucleotide exchange factors and GTPase-activating proteins (GAPs). GAPs accelerate GTP hydrolysis, playing a crucial role in modulating Ras signalling to prevent excessive or prolonged activation. Here, we investigated monofunctional azobenzene derivatives as photochromic modulators to control the function of Ras in a light-dependent and reversible manner. Three thiol-reactive azobenzene derivatives with distinct electrostatic properties were synthesized and incorporated into GAP functional sites to modulate Ras activity. GAP mutants containing a single cysteine residue at the functional site were generated using an Escherichia coli expression system. Our results showed that modifications near the GAP 'arginine finger', a critical region for stabilizing the GTP hydrolysis transition state of Ras, induced significant light-dependent changes in GTPase activity. We achieved photoreversible control of the interaction between Ras and its effector Raf using these azobenzene derivatives. These findings suggest that Ras function can be precisely modulated using photochromic molecules, providing a novel light-based approach for controlling Ras activity.</p>","PeriodicalId":15234,"journal":{"name":"Journal of biochemistry","volume":" ","pages":"363-374"},"PeriodicalIF":2.1,"publicationDate":"2025-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143390886","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":"NMR analysis of interaction between RNA structure elements and small molecules.","authors":"Megumi Tomemori, Rika Ichijo, Yoko Shinohara, Kaori Hatta, Kazuhiko Nakatani, Gota Kawai","doi":"10.1093/jb/mvaf020","DOIUrl":"https://doi.org/10.1093/jb/mvaf020","url":null,"abstract":"<p><p>RNA-targeted small molecule drug discovery is widely recognized as an important modality. However, not enough knowledge on the interaction between RNAs and small molecules is accumulated yet. In the present study, 46 RNAs were designed with various internal loops or hairpin loops based on a 29-mer model RNA. The interaction of designed RNAs and three kind of small molecules, risdiplam, naphthyridine carbamate dimer (NCD) and ciprofloxacin, were examined by NMR spectroscopy. The results of interaction experiments were quantitatively analyzed and RNAs interacting with the small molecules were selected. Among the three compounds, NCD shows relatively stronger affinity to some of the model RNAs as judged by the NMR spectra, and binding sites of NCD for two RNAs were determined. The measurement condition used in this work, including the annealing free sample preparation as well as the Mg2+ free sodium phosphate buffer, can be the standard for initial the NMR screening in the RNA-targeted small molecule drug discovery.</p>","PeriodicalId":15234,"journal":{"name":"Journal of biochemistry","volume":" ","pages":""},"PeriodicalIF":2.1,"publicationDate":"2025-04-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144002320","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":"Suicide substrate reaction-like modification of mouse serine racemase with L-serine.","authors":"Akari Hata, Tomokazu Ito, Hitoshi Mori, Takuya Ogawa, Tatsuo Kurihara, Hisashi Hemmi, Tohru Yoshimura","doi":"10.1093/jb/mvaf019","DOIUrl":"https://doi.org/10.1093/jb/mvaf019","url":null,"abstract":"<p><p>A pyridoxal 5'-phosphate-dependent fold-type II serine racemase (SR) is responsible for the synthesis of D-Ser, which serves as a co-agonist of N-methyl-D-aspartate glutamate receptor. In addition to racemization, SR catalyzes the dehydration of D- and L-Ser. SR is suggested to be involved in the D-Ser degradation in vivo, but this has not been confirmed. In this study, we found that mouse SR (mSR) underwent a suicide substrate reaction-like modification with its substrate, resulting in a remarkable change in its reaction specificity. mSR gradually lost its activity by the incubation with L- and D-Ser, but not completely. mSR was labelled with [14C]-L-Ser. ESI-MS analysis revealed that the molecular mass of SR increased by 84 Da by the incubation with L-Ser. Taken together with the results of previous crystallographic studies of fission yeast SR, we concluded that the active site lysine residue of mSR was modified with an α-aminoacrylate intermediate generated from L-Ser and converted to a lysinoalanine residue. The modification significantly decreased the racemization and L-Ser dehydration activities, while dramatically increased the D-Ser dehydration activity by the ~100 times reduction of the Km value. This is probably advantageous for the D-Ser degradation by mSR under physiological conditions.</p>","PeriodicalId":15234,"journal":{"name":"Journal of biochemistry","volume":" ","pages":""},"PeriodicalIF":2.1,"publicationDate":"2025-04-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143998817","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":"The potential of erythrocyte α-synuclein to differentiate dementia with Lewy bodies from Parkinson's and Alzheimer's diseases.","authors":"Ryosuke Amagai, Ryunosuke Hosoi, Sakura Yoshioka, Taiki Maruyama, Takayuki Kawai, Soroku Yagihashi, Hitoshi Nukada, Ryuji Sakakibara, Ayako Okado-Matsumoto","doi":"10.1093/jb/mvaf017","DOIUrl":"https://doi.org/10.1093/jb/mvaf017","url":null,"abstract":"<p><p>Dementia with Lewy bodies (DLB) is the second most common neurodegenerative dementia after Alzheimer's disease (AD). Early differentiation of these disorders is crucial for managing core symptoms; however, existing biomarkers remain insufficient. DLB shares motor and cognitive symptoms with Parkinson's disease (PD), and both are classified as synucleinopathies due to abnormal α-synuclein aggregation. Although α-synuclein is predominantly expressed in the central nervous system, it is also abundant in erythrocytes. Recent studies suggest a potential link between erythrocyte-derived α-synuclein and synucleinopathy pathology. Additionally, we previously reported that both erythrocytes and circulating medium and large extracellular vesicles (m/lEVs) in plasma from healthy subjects contain full-length and C-terminally truncated α-synuclein. In this study, we found that erythrocyte α-synuclein levels were significantly lower in DLB compared to AD, PD, and healthy controls. Furthermore, α-synuclein levels in circulating m/lEVs were elevated in patients with neurodegenerative diseases. These findings provide new insights into the role of peripheral α-synuclein and suggest its potential utility as a diagnostic marker for DLB. While further validation is needed, erythrocyte-derived α-synuclein may complement nuclear medicine assessments in distinguishing DLB from other neurodegenerative disorders.</p>","PeriodicalId":15234,"journal":{"name":"Journal of biochemistry","volume":" ","pages":""},"PeriodicalIF":2.1,"publicationDate":"2025-04-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144007450","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}
Chunyang Wang, Kai Huang, Jie Yang, Qingchun Xu, Jiagao Kuai, Guangxian Zhang, Xiaoming Wang
{"title":"YTHDF1 promotes pancreatic cancer cell progression by enhancing SF3B2 translation though m6A modification.","authors":"Chunyang Wang, Kai Huang, Jie Yang, Qingchun Xu, Jiagao Kuai, Guangxian Zhang, Xiaoming Wang","doi":"10.1093/jb/mvaf018","DOIUrl":"https://doi.org/10.1093/jb/mvaf018","url":null,"abstract":"<p><p>N6-Methyladenosine (m6A), a pivotal RNA modification, plays a critical role in carcinogenesis across multiple cancer types. YT521-B homology domain family protein 1 (YTHDF1), a binding protein of m6A, facilitates the translation of downstream targets via m6A recognition. However, the involvement of YTHDF1 in pancreatic cancer progression and its mechanistic underpinnings remain poorly understood. In this study, we observed significant upregulation of YTHDF1 in pancreatic cancer cell lines (SW1990 and PANC-1) compared to the normal human pancreatic cell line hTERT-HPNE. Functional assays revealed that YTHDF1 knockdown markedly suppressed cell proliferation and invasion, whereas its overexpression enhanced these malignant phenotypes in both SW1990 and PANC-1 cells. Mechanistically, YTHDF1 interacted with CDS region of splicing factor 3B subunit 2 (SF3B2), whereas YTHDF1 downregulation reduced SF3B2 protein levels without altering its mRNA expression, suggesting post-transcriptional regulation via m6A modification. Importantly, SF3B2 overexpression rescued the suppressed proliferation and invasion caused by YTHDF1 knockdown in SW1990 and PANC-1 cells. Collectively, our findings demonstrate that YTHDF1 drives pancreatic cancer progression by enhancing SF3B2 translation through m6A modification, thereby providing novel mechanistic insights and a potential therapeutic target for pancreatic cancer.</p>","PeriodicalId":15234,"journal":{"name":"Journal of biochemistry","volume":" ","pages":""},"PeriodicalIF":2.1,"publicationDate":"2025-04-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144002305","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":"Innate immune signals triggered on organelle membranes.","authors":"Yoshihiko Kuchitsu, Tomohiko Taguchi","doi":"10.1093/jb/mvaf016","DOIUrl":"https://doi.org/10.1093/jb/mvaf016","url":null,"abstract":"<p><p>Our body is constantly exposed to pathogens, and equipped with a highly elaborate immune system to fight against invading pathogens. The first line of defense is the innate immune system. It has evolved to detect conserved microbial molecular patterns, dubbed pathogen-associated molecular patterns (PAMPs), through pattern recognition receptors (PRRs). The binding of PRRs to PAMPs activates intracellular signalling cascades that lead to the expression of proinflammatory cytokines, type I interferons, and other antiviral proteins that all coordinate the elimination of pathogens and infected cells. PRRs can be classified as transmembrane receptors, including Toll-like receptors (TLRs) and some C-type lectin receptors (CLRs), and as cytosolic receptors including retinoic acid-inducible gene-I (RIG-I)-like receptors, nucleotide-binding domain and leucine-rich repeat-containing (NLR) proteins, and cyclic GMP-AMP (cGAMP) synthase (cGAS). Studies have revealed that innate immune signals, including the ones activated by cytosolic PRRs, are triggered on organelle membranes. Here we review the recent insights into how organelle membranes and their associated membrane lipids contribute to PRR-mediated innate immune signals.</p>","PeriodicalId":15234,"journal":{"name":"Journal of biochemistry","volume":" ","pages":""},"PeriodicalIF":2.1,"publicationDate":"2025-04-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143803377","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":"Identification of a novel Eps 15 homology domain-containing protein 1 (EHD1) and EHD4-binding motif in phostensin.","authors":"Kuang-Yung Huang, Hui-Chun Yu, Ming-Chi Lu, Hsien-Yu Huang Tseng, Jyun-Jie Shen, Chia-Ying Lin, Pin-Chen Chen, Ya-Ting Shen, Pei-Rong Chung, Hsiao-Kuei Tsai, Si-Ru Zhou, Chia-Lin Wang, Ning-Sheng Lai, Ta-Hsien Lin, Hsien-Bin Huang","doi":"10.1093/jb/mvaf002","DOIUrl":"10.1093/jb/mvaf002","url":null,"abstract":"<p><p>Phostensin (PTS) encoded by KIAA1949 binds to protein phosphatase 1, F-actin, Eps 15 homology domain-containing protein 1 (EHD1) and EHD4. Most EHD-binding proteins contain a consensus motif, Asn-Pro-Phe (NPF), which interacts with the C-terminal EH domain of EHD proteins. Nevertheless, the NPF motif is absent in PTS. The binding motif for PTS to interact with EHD1 (or EHD4) remains unknown. Here, we identified that PTS-α binds to EHD1 (or EHD4) through the region of residues 51-80, which contains a consensus motif, 64ILV(X)4(L/V)RL74S. This novel consensus motif is also found in vacuolar protein sorting-35 (vps35). Replacement of 64ILV(X)4(L/V)RL74S with 64AAA(X)4(L/V)RL74S or with 64ILV(X)4AEA74A significantly reduces the binding efficiency of PTS-α to either EHD1 or EHD4 in GST pull-down assay and far western blotting assay. In addition, replacement of 218ILV(X)4VRL228S with 218AAA(X)4AEA228A decreases the binding ability of vps35 to EHD4 in far western blotting assay. Overexpression of the PTS-β in 293 T cells attenuated the endocytic trafficking of transferrin. However, this attenuation of transferrin in endocytic trafficking was disrupted when 293 T cells overexpressed the mutant PTS-β with a defective EHD-binding motif, suggesting that PTS-β can regulate the endocytic recycling via associating with EHD1 or EHD4.</p>","PeriodicalId":15234,"journal":{"name":"Journal of biochemistry","volume":" ","pages":"297-304"},"PeriodicalIF":2.1,"publicationDate":"2025-04-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142949467","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}