Journal of biochemistry最新文献

Zinc-mediated structural and functional regulation of ERp44 and ERGIC-53 in protein quality control. 锌介导ERp44和ERGIC-53在蛋白质量控制中的结构和功能调控。

IF 1.7 4区生物学

Journal of biochemistry Pub Date : 2026-05-05 DOI: 10.1093/jb/mvag033

Satoshi Watanabe, Kenji Inaba

引用次数: 0

Endothelial RhoA is essential for embryonic and postnatal vascular development by regulating KLF2-Notch1 signaling. 内皮RhoA通过调节KLF2-Notch1信号传导对胚胎和出生后血管发育至关重要。

IF 1.7 4区生物学

Journal of biochemistry Pub Date : 2026-04-25 DOI: 10.1093/jb/mvag032

Wondwossen Wale Tesega, Akio Shimizu, Taha Hussain, Fumiya Sawasaki, Lucia Sugawara, Shoma Matsumoto, Masatsugu Ema, Akira Sato, Hisakazu Ogita

{"title":"Endothelial RhoA is essential for embryonic and postnatal vascular development by regulating KLF2-Notch1 signaling.","authors":"Wondwossen Wale Tesega, Akio Shimizu, Taha Hussain, Fumiya Sawasaki, Lucia Sugawara, Shoma Matsumoto, Masatsugu Ema, Akira Sato, Hisakazu Ogita","doi":"10.1093/jb/mvag032","DOIUrl":"https://doi.org/10.1093/jb/mvag032","url":null,"abstract":"The small GTPase RhoA has diverse cellular functions, including in actin fiber reorganization. However, its role in angiogenesis remains elusive. To reveal this, we generated mice with endothelium-specific constitutive or tamoxifen-inducible conditional knockout (cKO) of RhoA. Both constitutive and inducible RhoA cKO mice all died by embryonic day 11.5. They displayed severe abnormalities in cephalic plexus vasculature and intersomitic vessels. Inducible RhoA cKO mice also had abnormal lymphatic vessels at mid-stage embryogenesis, and showed significant reductions in radial outgrowth and density of vascular plexus in the retina on postnatal day 10. Blood flow recovery and vascular repair in ischemic hindlimbs were also impaired in adult inducible RhoA cKO mice. The expression of a stalk cell marker Notch1 was reduced, but that of a tip cell marker Dll4 was unchanged in the branched vessels of RhoA cKO embryos. By luciferase analysis and a database search, KLF2 was identified as a negative regulator of Notch1 expression by binding to the NOTCH1 gene promoter. KLF2 was phosphorylated by the RhoA-ROCK pathway, which inhibited KLF2 nuclear translocation, resulting in increases in Notch1 transcription and expression. Endothelial RhoA supports endothelial differentiation through KLF2-Notch1 signaling and promotes embryonic and postnatal vascular development.","PeriodicalId":15234,"journal":{"name":"Journal of biochemistry","volume":" ","pages":""},"PeriodicalIF":1.7,"publicationDate":"2026-04-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147772625","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

A two-tiered epigenetic mechanism ensures imprint stability after fertilization: insights from the Igf2/H19 locus. 一个双层的表观遗传机制确保受精后的印记稳定性：来自Igf2/H19位点的见解。

IF 1.7 4区生物学

Journal of biochemistry Pub Date : 2026-04-17 DOI: 10.1093/jb/mvag030

Hitomi Matsuzaki, Teruhito Ishihara, Keiji Tanimoto

{"title":"A two-tiered epigenetic mechanism ensures imprint stability after fertilization: insights from the Igf2/H19 locus.","authors":"Hitomi Matsuzaki, Teruhito Ishihara, Keiji Tanimoto","doi":"10.1093/jb/mvag030","DOIUrl":"https://doi.org/10.1093/jb/mvag030","url":null,"abstract":"Genomic imprinting is a crucial epigenetic mechanism directing parent-of-origin-specific gene expression in mammals, and it is regulated by allele-specific DNA methylation at imprinting control regions (ICRs). In this canonical imprinting mechanism, maintenance factors preserve germline-derived DNA methylation at ICRs during genome-wide demethylation after fertilization. However, our studies of the Igf2/H19 locus reveal that allele-specific de novo DNA methylation after fertilization, termed 'post-fertilization imprinted methylation,' also contributes to imprint maintenance. In this process, epigenetic imprints other than DNA methylation are thought to guide the recognition of parental alleles by de novo methyltransferases in the next generation, acting in concert with maintenance factors to ensure stable DNA methylation at canonical imprinted loci. Recently identified non-canonical imprinting, in contrast, relies on non-DNA methylation marks that are converted into DNA methylation only after implantation. Despite differences in the timing of this conversion, post-fertilization imprinted methylation may share similarities with non-canonical imprinting. Collectively, these findings suggest that the robustness of canonical imprinting is supported by a two-tiered regulatory system.","PeriodicalId":15234,"journal":{"name":"Journal of biochemistry","volume":" ","pages":""},"PeriodicalIF":1.7,"publicationDate":"2026-04-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147698858","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

Targeting the CCL2-CCR2 axis in cancer: insights from in vitro screening and humanized mice. 在癌症中靶向CCL2-CCR2轴：来自体外筛选和人源化小鼠的见解。

IF 1.7 4区生物学

Journal of biochemistry Pub Date : 2026-04-14 DOI: 10.1093/jb/mvag009

Yanjun Chen, Midori Shimada

{"title":"Targeting the CCL2-CCR2 axis in cancer: insights from in vitro screening and humanized mice.","authors":"Yanjun Chen, Midori Shimada","doi":"10.1093/jb/mvag009","DOIUrl":"https://doi.org/10.1093/jb/mvag009","url":null,"abstract":"An immunosuppressive tumor microenvironment that facilitates cancer progression is an important challenge in combating the disease. The CCL2-CCR2 axis is a primary facilitator in this process, facilitating the recruitment of CCR2-positive myeloid cells, including M-MDSCs and TAMs, to tumor and metastatic locations. CCR2 is also expressed on tumor cells and regulatory T cells, further enhancing cancer cell motility and immune suppression. Inhibition of this system through genetic deletion or small-molecule inhibitors significantly reduces primary tumor and metastasis in preclinical models, highlighting CCR2 as a promising therapeutic target. Although several CCR2 inhibitors have entered clinical trials, differences in their potency and the limited predictability of murine models have hampered clinical translation. The current work by Sugiyama et al. carefully evaluated 10 human CCR2 antagonists, identifying MK0812 as the most effective inhibitor. Using human CCR2B knock-in mice, they established a practical platform for evaluating CCR2-targeted drugs with direct relevance to human cancer therapy, highlighting the importance of humanized models for translational immuno-oncology.","PeriodicalId":15234,"journal":{"name":"Journal of biochemistry","volume":" ","pages":""},"PeriodicalIF":1.7,"publicationDate":"2026-04-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147690510","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

Dynamic Changes of the Sympathetic Nervous System in the Bone Marrow in Myeloid Leukemia. 骨髓性白血病患者骨髓交感神经系统的动态变化。

IF 1.7 4区生物学

Journal of biochemistry Pub Date : 2026-04-13 DOI: 10.1093/jb/mvag028

Sayumi Okigawa, Hibiki Inafuku, Ayuna Hattori, Takahiro Ito

{"title":"Dynamic Changes of the Sympathetic Nervous System in the Bone Marrow in Myeloid Leukemia.","authors":"Sayumi Okigawa, Hibiki Inafuku, Ayuna Hattori, Takahiro Ito","doi":"10.1093/jb/mvag028","DOIUrl":"https://doi.org/10.1093/jb/mvag028","url":null,"abstract":"Chronic myeloid leukemia (CML) is a hematologic malignancy originating from hematopoietic stem cells with the fusion oncogene BCR-ABL1 on the Philadelphia chromosome, which drives the abnormal proliferation of leukemic blast cells within the bone marrow microenvironment. While previous research has primarily focused on the hematopoietic compartment, the functional contribution of the bone marrow microenvironment to the CML pathology remains understudied. We investigated the changes in the peripheral nervous system in the bone marrow with myeloid leukemia via immunofluorescence staining of tyrosine hydroxylase (TH) and calcitonin gene-related peptide (CGRP) antibodies in mouse with NUP98-HOXA9- and BCR-ABL1-expressing myeloid leukemia. We found that the TH-positive fibers were significantly reduced, while no overt changes were observed in CGRP-positive nerves in the bone marrow. The reduction in TH-positive nerve cells was also evident in the spleen. Human patient gene expression data suggested that the levels of sympathetic nerve receptor expression change during the blastic transformation of human CML. Our findings indicate that the sympathetic nervous system regulates the pathogenesis of myeloid leukemia and could play a crucial role in the disease progression of myeloid leukemia.","PeriodicalId":15234,"journal":{"name":"Journal of biochemistry","volume":" ","pages":""},"PeriodicalIF":1.7,"publicationDate":"2026-04-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147673663","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

Observation of redistribution for local conformational dynamics in cross-reactive antibody design. 交叉反应抗体设计中局部构象动力学重分布的观察。

IF 1.7 4区生物学

Journal of biochemistry Pub Date : 2026-04-13 DOI: 10.1093/jb/mvag018

Yoshiki Yasuda, Satoru Nagatoishi, Jiei Sasaki, Ryo Matsunaga, Daisuke Kuroda, Takao Hashiguchi, Kouhei Tsumoto

{"title":"Observation of redistribution for local conformational dynamics in cross-reactive antibody design.","authors":"Yoshiki Yasuda, Satoru Nagatoishi, Jiei Sasaki, Ryo Matsunaga, Daisuke Kuroda, Takao Hashiguchi, Kouhei Tsumoto","doi":"10.1093/jb/mvag018","DOIUrl":"10.1093/jb/mvag018","url":null,"abstract":"Antibody engineering is often achieved through laborious mutagenesis and screening. However, the physicochemical basis of cross-reactivity-enhancing mutations remains unclear. We computationally redesigned the severe acute respiratory syndrome coronavirus (SARS-CoV)-1 neutralizing antibody m396 to recognize the SARS-CoV-2 receptor-binding domain (RBD) and characterized its biophysical properties. A first-generation variant carrying three light-chain substitutions (S30LW, S93LI and S94LF) acquired detectable SARS-CoV-2 RBD binding, while strengthening its affinity for the SARS-CoV RBD. A second-generation variant carrying two substitutions (T52HL and L54HW) further improved SARS-CoV-2 binding with a low micromolar affinity, predominantly driven by an approximately 200-fold increase in the association rate. Circular dichroism spectra indicated preserved global folding across the variants, whereas differential scanning calorimetry revealed stepwise decreases in lower-temperature unfolding transitions. Hydrogen-deuterium exchange mass spectrometry showed increased dynamics of CDR-L1 and localized rigidification near CDR-H2 in the second variant. These results suggest a biophysical model in which a small number of mutations reprogram cross-recognition by redistributing the local conformational dynamics.","PeriodicalId":15234,"journal":{"name":"Journal of biochemistry","volume":" ","pages":"259-267"},"PeriodicalIF":1.7,"publicationDate":"2026-04-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13064648/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147433123","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

Dynamics of CDKL5 phosphorylation and its regulatory mechanisms in cultured cells. CDKL5在培养细胞中的磷酸化动态及其调控机制。

IF 1.7 4区生物学

Journal of biochemistry Pub Date : 2026-04-10 DOI: 10.1093/jb/mvag029

Syouichi Katayama, Miwako Sakota, Atsushi Morii

{"title":"Dynamics of CDKL5 phosphorylation and its regulatory mechanisms in cultured cells.","authors":"Syouichi Katayama, Miwako Sakota, Atsushi Morii","doi":"10.1093/jb/mvag029","DOIUrl":"https://doi.org/10.1093/jb/mvag029","url":null,"abstract":"Cyclin-dependent kinase-like 5 (CDKL5) is a serine/threonine protein kinase highly expressed in the brain, and mutations in its gene cause CDKL5 deficiency disorder (CDD). Although reports on CDKL5 substrate proteins are increasing, the phosphorylation-dependent regulation of CDKL5 function remains poorly understood. Therefore, in this study, we investigated the phosphorylation states of CDKL5 and explored the kinases and phosphatases involved in its regulation. The C-terminal region of exogenous CDKL5 was highly phosphorylated in Neuro2a neuroblastoma cells; endogenous CDKL5 in P19 embryonic carcinoma (P19EC) cells was also highly phosphorylated, mainly in the cytoplasm. CDKL5 underwent gradual dephosphorylation during aggregate formation in P19EC cells, and this process was suppressed by retinoic acid (RA), an inducer of neuronal differentiation. Okadaic acid treatment indicated that protein phosphatase 2A (PP2A) partially mediates CDKL5 dephosphorylation during aggregate formation. Kinase inhibitor screening and kinase assay in vitro demonstrated that multiple protein kinase C (PKC) isoforms contribute to CDKL5 phosphorylation. These findings suggest that CDKL5 phosphorylation is dynamically regulated by a balance between PKC and PP2A activities, and that RA signaling modulates this process during neuronal differentiation. Such phosphorylation mechanisms of CDKL5 may underlie the pathogenesis of CDD and help identify potential therapeutic targets.","PeriodicalId":15234,"journal":{"name":"Journal of biochemistry","volume":" ","pages":""},"PeriodicalIF":1.7,"publicationDate":"2026-04-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147673719","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

Phosphatidylinositol 3,4-bisphosphate Emerges as a Lipid Mediator Linking Oxidative Stress to DNA Damage. 磷脂酰肌醇3,4-二磷酸作为脂质介质连接氧化应激和DNA损伤。

IF 1.7 4区生物学

Journal of biochemistry Pub Date : 2026-04-08 DOI: 10.1093/jb/mvag027

Yuto Kikuchi, Hiroaki Kajiho, Junya Hasegawa, Yuki Mochida, Satoshi Uchida, Junko Sasaki, Takehiko Sasaki

{"title":"Phosphatidylinositol 3,4-bisphosphate Emerges as a Lipid Mediator Linking Oxidative Stress to DNA Damage.","authors":"Yuto Kikuchi, Hiroaki Kajiho, Junya Hasegawa, Yuki Mochida, Satoshi Uchida, Junko Sasaki, Takehiko Sasaki","doi":"10.1093/jb/mvag027","DOIUrl":"https://doi.org/10.1093/jb/mvag027","url":null,"abstract":"Reactive oxygen species function as physiological signaling molecules but, when excessive, cause oxidative stress that damages DNA. Using quantitative phosphoinositide profiling by regioisomer-resolving mass spectrometry, we identified phosphatidylinositol 3,4-bisphosphate [PI(3,4)P₂] as a phosphoinositide class robustly induced by hydrogen peroxide (H₂O₂). Biochemical and genetic analyses demonstrated that stress-induced PI(3,4)P₂ production was predominantly dependent on the phosphoinositide 5-phosphatase Src homology 2 domain-containing inositol 5-phosphatase 2 (SHIP2). SHIP2 deficiency markedly suppressed PI(3,4)P₂ accumulation and reduced oxidative stress-induced DNA damage. Oxidative stress increased PI(3,4)P₂ levels in the nuclear fraction, and intracellular delivery of PI(3,4)P₂ was sufficient to induce DNA damage independently of oxidative stress. These findings identify PI(3,4)P₂ as a lipid mediator linking oxidative stress to genome instability and uncover a SHIP2-dependent remodeling pathway that connects redox perturbation to DNA damage responses.","PeriodicalId":15234,"journal":{"name":"Journal of biochemistry","volume":" ","pages":""},"PeriodicalIF":1.7,"publicationDate":"2026-04-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147645637","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

Regulatory dynamics of monosomes and polysomes in cellular adaptation. 细胞适应中单体和多体的调控动力学。

IF 1.7 4区生物学

Journal of biochemistry Pub Date : 2026-04-01 DOI: 10.1093/jb/mvag026

Hirotatsu Imai, Akio Yamashita

{"title":"Regulatory dynamics of monosomes and polysomes in cellular adaptation.","authors":"Hirotatsu Imai, Akio Yamashita","doi":"10.1093/jb/mvag026","DOIUrl":"https://doi.org/10.1093/jb/mvag026","url":null,"abstract":"Cytosolic 80S ribosomes have long been considered a uniform translation apparatus, with the only distinction being that they exist as either monosomes or polysomes. However, emerging evidence has revealed that monosomes and polysomes exhibit distinct translational profiles, contributing to selective protein synthesis and localized messenger RNA (mRNA) translation in specific subcellular compartments in mammals. When mammalian cells encounter environmental or metabolic stress, global gene expression is dynamically reprogrammed, accompanied by a marked shift in the monosome-to-polysome ratio, suggesting context-dependent roles for monosome- and polysome-mediated mRNA translation in cellular adaptation. In parallel, accumulating evidence indicates that distinct types of eukaryotic non-translating monosomes are formed under various biological conditions. Moreover, monosomes participate in the first round of mRNA translation on newly synthesized mRNAs, a process coupled with several early events such as nonsense-mediated mRNA decay and messenger ribonucleoprotein (mRNP) remodeling. In this review, we summarize current advances in understanding the roles of monosomes as crucial regulatory layers that shape the proteome across diverse physiological conditions in mammals.","PeriodicalId":15234,"journal":{"name":"Journal of biochemistry","volume":" ","pages":""},"PeriodicalIF":1.7,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147592329","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

DDX5: A Versatile RNA Helicase in Cancer and Cell Fate Determination-Linking c-Myc and JAK2 V617F Signaling to Emerging Therapeutics. DDX5：癌症和细胞命运决定中的多功能RNA解旋酶-将c-Myc和JAK2 V617F信号与新兴治疗方法联系起来

IF 1.7 4区生物学

Journal of biochemistry Pub Date : 2026-03-26 DOI: 10.1093/jb/mvag025

Kenji Tago, Megumi Funakoshi-Tago

{"title":"DDX5: A Versatile RNA Helicase in Cancer and Cell Fate Determination-Linking c-Myc and JAK2 V617F Signaling to Emerging Therapeutics.","authors":"Kenji Tago, Megumi Funakoshi-Tago","doi":"10.1093/jb/mvag025","DOIUrl":"https://doi.org/10.1093/jb/mvag025","url":null,"abstract":"Traditionally regarded as a DEAD-box RNA helicase involved in RNA metabolism, DDX5 (also known as p68) has emerged as a signal-responsive regulator that integrates RNA processing with transcriptional control, thereby influencing cell fate determination and tumorigenesis. Beyond its canonical roles in pre-mRNA splicing, ribosome biogenesis, microRNA maturation, and R-loop resolution, DDX5 also functions in a helicase-independent manner as a transcriptional co-activator for diverse transcription factors and signaling pathways. Recent studies have revealed a dichotomy in which the RNA helicase activity and scaffolding/co-activator functions of DDX5 are selectively deployed in a context-dependent manner. In cancer, DDX5 enhances the transcriptional activity and transforming capacity of the proto-oncogene c-Myc and is itself transcriptionally induced by c-Myc, forming a positive feedback loop that sustains oncogenic transcriptional programs. DDX5 is also indispensable for transformation driven by the constitutively active JAK2 V617F mutant, a major driver of myeloproliferative neoplasms, where it promotes malignant signaling largely independently of its RNA helicase activity. In contrast, during adipocyte differentiation, the helicase function of DDX5 is essential for glucocorticoid receptor transcriptional programs. Importantly, recent studies have identified the small-molecule compound FL118 as a potent DDX5 degrader, providing proof of concept that targeting DDX5 protein stability represents a promising therapeutic strategy.","PeriodicalId":15234,"journal":{"name":"Journal of biochemistry","volume":" ","pages":""},"PeriodicalIF":1.7,"publicationDate":"2026-03-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147512347","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