Journal of biochemistry最新文献_第3页

Proteomics and Synaptome Mapping to Uncover Diversity in Excitatory Synapses. 蛋白质组学和突触组图谱揭示兴奋性突触的多样性。

IF 2.4 4区生物学

Journal of biochemistry Pub Date : 2026-07-20 DOI: 10.1093/jb/mvag056

Takeshi Kaizuka

{"title":"Proteomics and Synaptome Mapping to Uncover Diversity in Excitatory Synapses.","authors":"Takeshi Kaizuka","doi":"10.1093/jb/mvag056","DOIUrl":"https://doi.org/10.1093/jb/mvag056","url":null,"abstract":"Synapses are the fundamental computational units of the brain. Although synapses are classically classified according to the neurotransmitter they use, glutamatergic excitatory synapses also exhibit marked heterogeneity in their molecular composition and structure. Understanding this diversity requires comprehensive approaches that go beyond small-scale, candidate-based analyses of synapses. Proteomic analyses of biochemically enriched synaptic fractions have provided unbiased, quantitative measurements of synaptic protein composition, revealing differences across brain regions, cell types, developmental stages, and physiological and pathological states. Proteomics has also revealed the composition and remodeling of synaptic protein complexes and post-translational modifications. In parallel, synaptome mapping, an imaging-based approach for the large-scale in situ analysis of synapses across the brain, has emerged as a form of spatial omics. In this approach, synapses labeled with a small set of synaptic proteins are systematically imaged across the brain. Synaptome mapping reveals whole-brain variation in synapse molecular identity and structural features, including differences in synapse size, shape, and spatial distribution in vivo. Together, these approaches show that excitatory synapses are diversified across anatomical, cellular, developmental, activity-dependent, and disease-related contexts. These complementary perspectives will advance our understanding of the synaptic mechanisms underlying neural computation, behavior, and brain disorders.","PeriodicalId":15234,"journal":{"name":"Journal of biochemistry","volume":" ","pages":""},"PeriodicalIF":2.4,"publicationDate":"2026-07-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148536013","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

ATP-generating activity of the ADP-forming acetyl-CoA synthetase in free-living microaerophilic fornicates, Aduncisulcus paluster and Kipferlia bialata. 自由生活的嗜氧小蚁、灰杉和木蕨中adp形成乙酰辅酶a合成酶的atp生成活性。

IF 2.4 4区生物学

Journal of biochemistry Pub Date : 2026-07-17 DOI: 10.1093/jb/mvag055

Toshitaka Koganemaru, Yoshitaka Tamura, Yasutaka Hoshi, Keitaro Kume, Tetsuo Hashimoto, Takeshi Nara

{"title":"ATP-generating activity of the ADP-forming acetyl-CoA synthetase in free-living microaerophilic fornicates, Aduncisulcus paluster and Kipferlia bialata.","authors":"Toshitaka Koganemaru, Yoshitaka Tamura, Yasutaka Hoshi, Keitaro Kume, Tetsuo Hashimoto, Takeshi Nara","doi":"10.1093/jb/mvag055","DOIUrl":"https://doi.org/10.1093/jb/mvag055","url":null,"abstract":"Fornicata is a group of eukaryotes adapted to anaerobic and microaerophilic environments. These organisms generate ATP anaerobically through substrate-level phosphorylation. ADP-forming acetyl-CoA synthetase (ACS) is one of the key enzymes of this process. While ACS characteristics in the parasite Giardia intestinalis have been studied, those in free-living species remain unknown. Here, we investigated the ATP-generating activities of recombinant ACS (rACS) of free-living fornicates Aduncisulcus paluster and Kipferlia bialata and compared them with Gasterophilus intestinalis. All rACSs exhibited the highest activity toward the substrate acetyl-CoA and the next toward n-propionyl-CoA. For acetyl-CoA, rApACS exhibited higher affinity (lower KM) and lower catalytic turnover (kcat) than the other two that displayed comparable kinetic profiles. For n-propionyl-CoA, rApACS also exhibited lower KM and kcat than the other two, while rGiACS exhibited far higher kcat than the other two, indicating that rGiACS could utilize n-propionyl-CoA effectively. For the substrate ADP, rKbACS exhibited the highest kcat among the three. These results suggest that ACSs from free-living fornicates are active ATP-generating enzymes, and that during the evolution of fornicates, the ATP-generating activity has been conserved, while the subtle changes in kinetic properties have occurred on their ACSs.","PeriodicalId":15234,"journal":{"name":"Journal of biochemistry","volume":" ","pages":""},"PeriodicalIF":2.4,"publicationDate":"2026-07-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148470894","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

Preferential formation of Nω-(carboxyethyl)arginine from methylglyoxal and its accumulation in human lens proteins. 甲基乙二醛优先形成Nω-（羧乙基）精氨酸及其在人晶状体蛋白中的积累。

IF 2.4 4区生物学

Journal of biochemistry Pub Date : 2026-07-15 DOI: 10.1093/jb/mvag053

Himeno Takahashi, Mime Nagai, Tsuyoshi Ikeda, Ken Hoshiyama, Takao Hirano, Toshinori Murata, Ryoji Nagai

{"title":"Preferential formation of Nω-(carboxyethyl)arginine from methylglyoxal and its accumulation in human lens proteins.","authors":"Himeno Takahashi, Mime Nagai, Tsuyoshi Ikeda, Ken Hoshiyama, Takao Hirano, Toshinori Murata, Ryoji Nagai","doi":"10.1093/jb/mvag053","DOIUrl":"https://doi.org/10.1093/jb/mvag053","url":null,"abstract":"Methylglyoxal (MGO), a highly reactive dicarbonyl compound generated mainly by glycolysis, is a major precursor of advanced glycation end products (AGEs). Although lysine-derived AGEs, such as Nε-(carboxyethyl)lysine (CEL), have been widely used as markers of MGO-mediated protein modification, increasing evidence suggests that MGO preferentially modifies arginine residues. However, the biochemical significance of arginine-derived AGEs remains poorly understood because of limited analytical and immunochemical methods for their detection. In this study, we investigated the formation and quantitative significance of Nω-(carboxyethyl)arginine (CEA), an underexplored MGO-derived arginine adduct. CEA was chemically synthesized and structurally characterized by NMR and mass spectrometry. Analysis of human tissues revealed that CEA accumulated at high levels in cataractous lenses, comparable to MG-H1 and higher than CEL levels. A monoclonal antibody specific for CEA was developed and validated using ELISA, showing no cross-reactivity with related AGEs. CEA was generated in a time-dependent manner in bovine serum albumin incubated with MGO, whereas CEL formation was minimal. CEA levels were higher than those of CEL in MGO-modified proteins, indicating its preferential formation under physiological conditions. These findings indicate that CEA is a reliable marker for evaluating MGO-mediated protein degeneration and dicarbonyl stress in vitro and in vivo.","PeriodicalId":15234,"journal":{"name":"Journal of biochemistry","volume":" ","pages":""},"PeriodicalIF":2.4,"publicationDate":"2026-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148455815","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

Replacement of non-canonical interloop disulfide bond of alpaca VHH by hydrophobic amino acids. 疏水氨基酸取代羊驼VHH非规范环间二硫键。

IF 2.4 4区生物学

Journal of biochemistry Pub Date : 2026-07-14 DOI: 10.1093/jb/mvag054

Yoko Akazawa-Ogawa, Lilian Kaede Komaba, Hideki Watanabe, Norihiko Kiyose, Nobuo Miyazaki, Tetsuo Fukuta, Yuji Ito, Tomonari Matsuda, Yoshihisa Hagihara

{"title":"Replacement of non-canonical interloop disulfide bond of alpaca VHH by hydrophobic amino acids.","authors":"Yoko Akazawa-Ogawa, Lilian Kaede Komaba, Hideki Watanabe, Norihiko Kiyose, Nobuo Miyazaki, Tetsuo Fukuta, Yuji Ito, Tomonari Matsuda, Yoshihisa Hagihara","doi":"10.1093/jb/mvag054","DOIUrl":"https://doi.org/10.1093/jb/mvag054","url":null,"abstract":"Non-canonical disulfide bonds are a hallmark of the VHH domain of heavy-chain antibodies, with predominant bonds between CDRs 1 and 3 and between framework FR2 and CDR3. The former interloop disulfide bond is advantageous for stability and antigen-binding affinity, albeit not indispensable. Importantly, mutations in the cysteine of the interloop disulfide bond of CDRs 1 and 3 can sometimes preserve antigen-binding activity. In contrast, the functional role of the interloop disulfide bond between FR2 and CDR3 remains largely understudied. In this study, we investigated the replacement of the disulfide bond between FR2 and CDR3 with cysteine mutations in aliphatic amino acids (alanine, valine, and isoleucine). These results indicate that this interloop disulfide bond contributes to the structural stabilization of VHH but is not required for antigen binding, consistent with the findings for the disulfide bond between CDRs 1 and 3. Furthermore, the disulfide bond between FR2 and CDR3 was not critical for maintaining reversibility following heat-induced unfolding. Given the prevalence of FR2-CDR3 interloop disulfide bonds in VHHs from llamas and alpacas, these findings provide valuable insights into VHH engineering and applications.","PeriodicalId":15234,"journal":{"name":"Journal of biochemistry","volume":" ","pages":""},"PeriodicalIF":2.4,"publicationDate":"2026-07-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148446968","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 leukaemia. 骨髓性白血病患者骨髓交感神经系统的动态变化。

IF 2.4 4区生物学

Journal of biochemistry Pub Date : 2026-07-01 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 leukaemia.","authors":"Sayumi Okigawa, Hibiki Inafuku, Ayuna Hattori, Takahiro Ito","doi":"10.1093/jb/mvag028","DOIUrl":"10.1093/jb/mvag028","url":null,"abstract":"Chronic myeloid leukaemia (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 leukaemia via immunofluorescence staining of tyrosine hydroxylase (TH) and calcitonin gene-related peptide (CGRP) antibodies in mouse with NUP98-HOXA9- and BCR-ABL1-expressing myeloid leukaemia. We found that the TH-positive fibres 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 leukaemia and could play a crucial role in the disease progression of myeloid leukaemia.","PeriodicalId":15234,"journal":{"name":"Journal of biochemistry","volume":" ","pages":"75-82"},"PeriodicalIF":2.4,"publicationDate":"2026-07-01","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

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 2.4 4区生物学

Journal of biochemistry Pub Date : 2026-07-01 DOI: 10.1093/jb/mvag027

Yuto Kikuchi, Hiroaki Kajiho, Junya Hasegawa, Jumpei Norimatsu, 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, Jumpei Norimatsu, Yuki Mochida, Satoshi Uchida, Junko Sasaki, Takehiko Sasaki","doi":"10.1093/jb/mvag027","DOIUrl":"10.1093/jb/mvag027","url":null,"abstract":"Reactive oxygen species function as physiological signalling 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. 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 remodelling pathway that connects redox perturbation to DNA damage responses.","PeriodicalId":15234,"journal":{"name":"Journal of biochemistry","volume":" ","pages":"21-31"},"PeriodicalIF":2.4,"publicationDate":"2026-07-01","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

DDX5: a versatile RNA helicase in cancer and cell fate determination-linking c-Myc and JAK2 V617F signalling 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 2.4 4区生物学

Journal of biochemistry Pub Date : 2026-07-01 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 signalling to emerging therapeutics.","authors":"Kenji Tago, Megumi Funakoshi-Tago","doi":"10.1093/jb/mvag025","DOIUrl":"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 tumourigenesis. 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 signalling 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 signalling 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":"1-10"},"PeriodicalIF":2.4,"publicationDate":"2026-07-01","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

Quantification of L- and D-enantiomers of proline, trans-4-hydroxyproline and cis-4-hydroxyproline in natural samples using differential labelling with 12C- and 13C6-dabsyl chloride, chiral separation and liquid chromatography-mass spectrometry. 用12C-和13c6 -达西氯鉴别标记、手性分离和液相色谱-质谱法定量天然样品中脯氨酸、反式-4-羟基脯氨酸和顺式-4-羟基脯氨酸的L-和d -对映体。

IF 2.4 4区生物学

Journal of biochemistry Pub Date : 2026-07-01 DOI: 10.1093/jb/mvag020

Bhisma Rai, Tetsuo Ishida

{"title":"Quantification of L- and D-enantiomers of proline, trans-4-hydroxyproline and cis-4-hydroxyproline in natural samples using differential labelling with 12C- and 13C6-dabsyl chloride, chiral separation and liquid chromatography-mass spectrometry.","authors":"Bhisma Rai, Tetsuo Ishida","doi":"10.1093/jb/mvag020","DOIUrl":"10.1093/jb/mvag020","url":null,"abstract":"L-Proline (L-Pro) and trans-4-hydroxy-L-proline (t-4-HPL) are major components of collagen and plant cell wall proteins. During their breakdown, free L-Pro and t-4-HPL are produced abundantly and play unique biological roles through complex metabolisms including isomerization. Therefore, it is essential to quantify all the six stereoisomers of proline and 4-hydroxyproline. Here, analytes were first labelled with 12C-dabsyl group, which has strong red colour and stability under light. Secondly, each of the 13C6-dabsyl stereoisomers were added to 12C-dabsylated samples as internal standards before cleanup. Finally, the molar ratio of 12C- and 13C6-dabsyl analytes was determined as the intensity ratio of doublet molecular ions with m/z difference of six in mass spectra, which were obtained by subjecting the cleaned sample to capillary chromatography-mass spectrometry. The total amounts of proline, t-4-HP and cis-4-hydroxyproline were determined using the standard addition method. Linear calibration curves (R2 > 0.99) were obtained in the range of 10-1000 pmol. To determine the molar ratio of D- and L-enantiomers, enantiopure dabsyl analyte fraction was obtained using reverse-phase and chiral chromatography. Mouse serum contained 0.20 μmol/L trans-4-hydroxy-D-proline. Achatina fulica haemolymph contained 0.070 μmol/L D-proline. The Santalum album wood powder contained all the 6 stereoisomers and unexpectedly the D-enantiomer was dominant for trans-4-hydroxyproline.","PeriodicalId":15234,"journal":{"name":"Journal of biochemistry","volume":" ","pages":"33-48"},"PeriodicalIF":2.4,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13326756/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147365391","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

IF 2.4 4区生物学

Journal of biochemistry Pub Date : 2026-07-01 DOI: 10.1093/jb/mvag049

Xiaohui Liu, Kaisei Koga, Masahiro Noguchi, Manato Hirata, Yuya Yasukochi, Kazuhiro Nagahama

{"title":"Estrogen-related receptor γ functions as a novel corepressor of androgen receptor by destabilizing receptor conformation and blocking coactivator recruitment.","authors":"Xiaohui Liu, Kaisei Koga, Masahiro Noguchi, Manato Hirata, Yuya Yasukochi, Kazuhiro Nagahama","doi":"10.1093/jb/mvag049","DOIUrl":"https://doi.org/10.1093/jb/mvag049","url":null,"abstract":"Estrogen-related receptor γ (ERRγ) is an orphan nuclear receptor whose molecular functions in transcriptional regulation remain incompletely understood. The androgen receptor (AR) is a ligand-dependent transcription factor that plays a pivotal role in prostate cancer by regulating gene expression through androgen-response elements. Its activity is tightly controlled by receptor conformation and coactivator recruitment. Although ERRγ has been implicated in the suppression of prostate cancer progression, whether it modulates AR signaling remains unclear. In this study, we examined the functional and molecular interplay between ERRγ and AR using a heterologous expression system in HeLa cells. We found that ERRγ suppresses AR-mediated transcriptional activation in a dose-dependent manner on ARE-containing promoters. Mechanistically, ERRγ interacted with ligand-activated AR in the nucleus and disrupted the intramolecular interaction between the N-terminal domain (NTD) and the C-terminal ligand-binding domain (LBD), which is required for full receptor activation. This interference did not affect AR nuclear translocation. Furthermore, ERRγ functionally competed with major transcriptional coactivators, including steroid receptor coactivators-3 (SRC-3) and p300, thereby attenuating coactivator-enhanced AR-dependent transcription. Collectively, these findings demonstrate that ERRγ functions as a novel corepressor of AR by destabilizing receptor conformation and blocking coactivator recruitment, providing new mechanistic insights into the regulation of AR-mediated transcription.","PeriodicalId":15234,"journal":{"name":"Journal of biochemistry","volume":" ","pages":""},"PeriodicalIF":2.4,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148360934","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

Recurrent mutations in protein tyrosine phosphatase receptor-type kappa in depressed-type colorectal carcinomas. 蛋白酪氨酸磷酸酶受体Kappa （PTPRK）在抑郁型结直肠癌中的复发性突变

IF 2.4 4区生物学

Journal of biochemistry Pub Date : 2026-07-01 DOI: 10.1093/jb/mvag024

Masayuki Tojo, Keiko Shinjo, Fumiharu Ohka, Keisuke Katsushima, Akira Hatanaka, Norihisa Ichimura, Hiromu Suzuki, Hisako Nozawa, Hitoshi Yoshida, Kazuo Konishi, Yutaka Kondo

{"title":"Recurrent mutations in protein tyrosine phosphatase receptor-type kappa in depressed-type colorectal carcinomas.","authors":"Masayuki Tojo, Keiko Shinjo, Fumiharu Ohka, Keisuke Katsushima, Akira Hatanaka, Norihisa Ichimura, Hiromu Suzuki, Hisako Nozawa, Hitoshi Yoshida, Kazuo Konishi, Yutaka Kondo","doi":"10.1093/jb/mvag024","DOIUrl":"10.1093/jb/mvag024","url":null,"abstract":"Genetic and epigenetic alterations in colorectal cancer (CRC) have been extensively investigated. Small depressed-type colorectal tumours (DCs) constitute a highly invasive CRC subtype. We characterized the mutational profiles of 22 DC samples, seven of which were subjected to whole exome sequencing. This revealed frequent mutations (7 of 22 cases, 31.8%) in PTPRK, with most of these mutations located in the D1 domain-encoding region. To further quantify the incidence of PTPRK mutations, we analysed 567 CRCs cases from two public databases (The Cancer Genome Atlas and the Catalogue of Somatic Mutations in Cancer). Mutations were more frequently observed in proximal colon tumours and were highly associated with the CpG island methylator phenotype-positive (CIMP-P) subtype (76.2%) and microsatellite instability (MSI; 66.7%). PTPRK mutant proteins (particularly those with D1 domain) retained the ability to bind integrin beta-4 (ITGB4). In addition, CRC cells expressing PTPRK mutants exhibited increased ITGB4 phosphorylation, suggesting that the mutations impair the phosphatase activity of PTPRK. Consistent with this, tumours with PTPRK mutations proliferated significantly more rapidly than their wild-type counterparts in vivo. These findings suggest that PTPRK mutations contribute to DC development by dysregulating phosphorylation-mediated signalling pathways.","PeriodicalId":15234,"journal":{"name":"Journal of biochemistry","volume":" ","pages":"49-63"},"PeriodicalIF":2.4,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13633085/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147443609","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