Biochemical Journal最新文献_第7页

Sequence rules for a long SPOP-binding degron required for protein ubiquitylation. 蛋白质泛素化所需的长spop结合降解的序列规则。

IF 4.3 3区生物学

Biochemical Journal Pub Date : 2025-05-21 DOI: 10.1042/BCJ20253041

Linda Makhlouf, Mukul Mishra, Hannah Makhlouf, Iain Manfield, Luca Busino, Elton Zeqiraj

{"title":"Sequence rules for a long SPOP-binding degron required for protein ubiquitylation.","authors":"Linda Makhlouf, Mukul Mishra, Hannah Makhlouf, Iain Manfield, Luca Busino, Elton Zeqiraj","doi":"10.1042/BCJ20253041","DOIUrl":"10.1042/BCJ20253041","url":null,"abstract":"The adaptor protein, speckle-type BTB/POZ protein (SPOP), recruits substrates to the cullin-3-subclass of E3 ligase for selective protein ubiquitylation. The Myddosome protein, myeloid differentiation primary response 88 (MyD88), is ubiquitylated by the SPOP-based E3 ligase to negatively regulate immune signaling; however, the sequence rules for SPOP-mediated substrate engagement and degradation are not fully understood. Here, we show that MyD88 interacts with SPOP through a long degron that contains the established SPOP-binding consensus and an N-terminal site that we name the Q-motif. Based on the sequence similarity to MyD88, we show that additional substrates, including steroid receptor coactivator-3, SET domain-containing protein 2, and Caprin1, engage SPOP in this manner. We show that the Q-motif is a critical determinant of these interactions in mammalian cells and determine X-ray crystal structures that show the molecular basis of SPOP associations with these proteins. These studies reveal a new consensus sequence for substrate-binding to SPOP that is necessary for substrate ubiquitylation, thus expanding the sequence rules required for SPOP-mediated E3 ligase substrate recognition.","PeriodicalId":8825,"journal":{"name":"Biochemical Journal","volume":" ","pages":"583-600"},"PeriodicalIF":4.3,"publicationDate":"2025-05-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7618200/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143771251","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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

The biology of interleukin-6 family cytokines is regulated by glycosylation. 白细胞介素-6家族细胞因子受糖基化调控。

IF 4.4 3区生物学

Biochemical Journal Pub Date : 2025-05-21 DOI: 10.1042/BCJ20240769

Lisa Kohrs, Falk F R Buettner, Juliane Lokau, Christoph Garbers

{"title":"The biology of interleukin-6 family cytokines is regulated by glycosylation.","authors":"Lisa Kohrs, Falk F R Buettner, Juliane Lokau, Christoph Garbers","doi":"10.1042/BCJ20240769","DOIUrl":"10.1042/BCJ20240769","url":null,"abstract":"Cytokines of the interleukin-6 (IL-6) family are important soluble mediators with crucial roles in developmental processes, tissue homeostasis, regeneration, and immune cell differentiation. Overshooting activities of IL-6 and other cytokines are found in all inflammatory diseases, making them attractive therapeutic targets for the treatment of patients with rheumatoid arthritis or inflammatory bowel disease. Multiple mechanisms exist that control cytokine activity and prevent excessive cytokine signaling under normal conditions. In this review, we summarize how the biology of IL-6 family cytokines is regulated by glycosylation, a process in which carbohydrate chains are covalently linked to protein molecules. The attached carbohydrates, which are generated and modified by enzymes located in the endoplasmic reticulum and/or the Golgi apparatus, can display huge structural diversity and are linked either via asparagine (N-glycans), serine and threonine (O-glycans), or tryptophan residues (C-glycans). We describe how glycosylation affects synthesis, receptor binding, signaling and plasma half-life of the cytokines and protein stability, transport to the cell surface, ligand binding, proteolysis, internalization, and recycling of their receptors. Finally, we discuss how knowledge about glycosylation can be used for the design of novel therapeutics targeting IL-6 family cytokines or their receptors.","PeriodicalId":8825,"journal":{"name":"Biochemical Journal","volume":"482 10","pages":"535-551"},"PeriodicalIF":4.4,"publicationDate":"2025-05-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12179393/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144641648","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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

Correction: Endogenous Rab29 does not impact basal or stimulated LRRK2 pathway activity. 更正：内源性Rab29不影响基础或刺激的LRRK2途径活性。

IF 4.3 3区生物学

Biochemical Journal Pub Date : 2025-05-21 DOI: 10.1042/BCJ20200458_COR

引用次数: 0

Cardiac substrate metabolism in type 2 diabetes. 2型糖尿病的心脏底物代谢。

IF 4.4 3区生物学

Biochemical Journal Pub Date : 2025-05-21 DOI: 10.1042/BCJ20240189

Jordan S F Chan, Tanin Shafaati, John R Ussher

{"title":"Cardiac substrate metabolism in type 2 diabetes.","authors":"Jordan S F Chan, Tanin Shafaati, John R Ussher","doi":"10.1042/BCJ20240189","DOIUrl":"10.1042/BCJ20240189","url":null,"abstract":"As the most metabolically demanding organ on a per gram basis, substrate metabolism in the heart is intricately linked to cardiac function. Virtually all major cardiovascular pathologies are associated with perturbations in cardiac substrate metabolism, and increasing evidence supports that these perturbations in substrate metabolism can directly contribute to cardiac dysfunction. Furthermore, type 2 diabetes (T2D) is a major risk factor for increased cardiovascular disease burden, while also being characterized by a very distinct metabolic profile in the heart. This includes increases in cardiac fatty oxidation rates and a robust reduction in cardiac glucose oxidation rates. Herein, we will describe the primary mechanisms responsible for the increase in cardiac fatty acid oxidation and decrease in cardiac glucose oxidation during T2D, while also detailing perturbations in cardiac ketone and amino acid metabolism. In addition, we will interrogate preclinical studies that have addressed whether correcting perturbations in cardiac substrate metabolism may have clinical utility against ischemic heart disease, diabetic cardiomyopathy, or heart failure associated with T2D. Lastly, we will consider the translational potential of such an approach to manage cardiovascular disease in people living with T2D.","PeriodicalId":8825,"journal":{"name":"Biochemical Journal","volume":"482 10","pages":"499-518"},"PeriodicalIF":4.4,"publicationDate":"2025-05-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12203942/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144641646","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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

Excess Wnt in neurological disease. 神经疾病中过量的Wnt。

IF 4.4 3区生物学

Biochemical Journal Pub Date : 2025-05-16 DOI: 10.1042/BCJ20240265

Danielle M Pascual, Delaram Jebreili Rizi, Harsimran Kaur, Paul C Marcogliese

{"title":"Excess Wnt in neurological disease.","authors":"Danielle M Pascual, Delaram Jebreili Rizi, Harsimran Kaur, Paul C Marcogliese","doi":"10.1042/BCJ20240265","DOIUrl":"10.1042/BCJ20240265","url":null,"abstract":"Wnt pathways are critical developmental signaling cascades that are conserved across multicellular life. A clear role for Wnt signaling in proper neural development has been well-established, yet less is known about its sustained expression and signaling in the mature nervous system. The precise role for Wnt pathways, canonical or otherwise, and individual Wnt components (ligands, receptors, transducers, effectors, and regulators) in the mature brain are poorly understood. However, genetic evidence implicating Wnt-related components in both neurodevelopmental and neurodegenerative disorders suggests that fine-tuned regulation of Wnt signaling is required for proper nervous system development and long-term homeostasis. Much has been documented about down-regulated Wnt signaling and its association with neurological conditions. Hence, the focus of this review is to consolidate and highlight the evidence for up-regulated Wnt transcription and/or signaling in neurodevelopmental and neurodegenerative disorders with a brief discussion on the role of deregulated Wnt in cancer. Finally, we touch upon the therapeutic prospect of Wnt inhibition in the nervous system.","PeriodicalId":8825,"journal":{"name":"Biochemical Journal","volume":"482 10","pages":""},"PeriodicalIF":4.4,"publicationDate":"2025-05-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12203940/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144075787","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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

Multifaceted roles of Epac signaling in renal functions. Epac信号在肾功能中的多重作用。

IF 4.1 3区生物学

Biochemical Journal Pub Date : 2025-05-14 DOI: 10.1042/bcj20253103

Oleh Pochynyuk,Kyrylo Pyrshev,Xiaodong Cheng

引用次数: 0

GPCR signaling via cAMP nanodomains. 通过cAMP纳米结构域的GPCR信号传导。

IF 4.4 3区生物学

Biochemical Journal Pub Date : 2025-05-13 DOI: 10.1042/BCJ20253088

Rahul Yadav, Manuela Zaccolo

{"title":"GPCR signaling via cAMP nanodomains.","authors":"Rahul Yadav, Manuela Zaccolo","doi":"10.1042/BCJ20253088","DOIUrl":"10.1042/BCJ20253088","url":null,"abstract":"G protein-coupled receptors (GPCRs) are the largest family of cell surface receptors, mediating essential physiological responses through diverse intracellular signaling pathways. When coupled to Gs or Gi proteins, GPCR modulates the synthesis of 3'-5'-cyclic adenosine monophosphate (cAMP), which governs a wide array of processes, ranging from cellular growth and survival to metabolic regulation. Studies have highlighted that cAMP is not uniformly distributed within cells but instead is compartmentalized into highly localized nanodomains. These nanodomains, mostly regulated by phosphodiesterases (PDEs), play a critical role in enabling signal precision and functional effects that are specific to individual stimuli. GPCRs can initiate distinct cAMP responses based on their localization within the cell, with evidence showing that both receptors resident at the plasma membrane and intracellular receptors-including endosomal, Golgi, and nuclear GPCRs-elicit unique cAMP signaling profiles. This review examines the mechanisms underlying GPCR signaling through cAMP nanodomains. We focus on the role of PDE-mediated cAMP degradation in shaping local cAMP signals, the emerging views on mechanisms that may contribute to signal compartmentalization, and the role of intracellular membrane compartments. By exploring these aspects, we aim to highlight the complexity of GPCR signaling networks and illustrate some of the implications for the regulation of cellular function.","PeriodicalId":8825,"journal":{"name":"Biochemical Journal","volume":"482 10","pages":""},"PeriodicalIF":4.4,"publicationDate":"2025-05-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12203925/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143955835","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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

The ascent of AKAPs, from architectural elements to kinase anchors: a perspective. akap的上升，从建筑元素到激酶锚：一个视角。

IF 4.1 3区生物学

Biochemical Journal Pub Date : 2025-05-13 DOI: 10.1042/bcj20253085

Jerome I Falcone,John D Scott

引用次数: 0

Basic features of cellular inositol metabolism as revealed by a newly developed LC-MS method. 新建立的LC-MS方法揭示了细胞肌醇代谢的基本特征。

IF 4.1 3区生物学

Biochemical Journal Pub Date : 2025-05-13 DOI: 10.1042/bcj20253028

Xue Bessie Su,Valeria Fedeli,Guizhen Liu,Meike Amma,Paraskevi Boulasiki,Jingyi Wang,Mariano Bizzarri,Henning Jessen,Dorothea Fiedler,Antonella Riccio,Adolfo Saiardi

{"title":"Basic features of cellular inositol metabolism as revealed by a newly developed LC-MS method.","authors":"Xue Bessie Su,Valeria Fedeli,Guizhen Liu,Meike Amma,Paraskevi Boulasiki,Jingyi Wang,Mariano Bizzarri,Henning Jessen,Dorothea Fiedler,Antonella Riccio,Adolfo Saiardi","doi":"10.1042/bcj20253028","DOIUrl":"https://doi.org/10.1042/bcj20253028","url":null,"abstract":"Inositol plays key roles in many cellular processes. Several studies focussed on the quantitative analysis of phosphorylated forms of inositol, enabled by analytical tools developed to detect these highly charged molecules. Direct measurement of free inositol however has been challenging, because the molecule is uncharged and polar. As a result, the mechanisms maintaining the homeostasis of the inositol remains poorly understood. In this study, we overcome these challenges by developing a quantitative liquid chromatography - mass spectrometry (LC-MS) protocol that can resolve and quantify the three main sugar molecules present inside cells: glucose, fructose, and inositol, as well as distinguish the clinically relevant isomers of inositol: myo-, scyllo-, and chiro-inositol. The quantitative power of the new method was validated by accurately monitoring the changes of inositol levels under well-established conditions in Saccharomyces cerevisiae, where the endogenous synthesis of inositol is increased in the transcription repressor OPI1 knockout opi1D and decreased when wild type yeast is fed with exogenous inositol. The method also revealed a new layer of regulation that takes place when exogenous inositol is added to further boost endogenous inositol synthesis in opi1D in a positive feedback loop. Analyses of mammalian cell lines provided many new insights into inositol metabolism. First, different cell lines displayed distinct sugar profiles and inositol concentrations and responded differently to inositol starvation. Second, mammalian cells can synthesize and import scyllo- but not chiro-inositol. Importantly, our method lent direct evidence to the previous hypothesis that lithium treatment could significantly reduce inositol levels in primary cortical neurons, thus diminishing the pool of free inositol available to the phosphoinositide cycle.","PeriodicalId":8825,"journal":{"name":"Biochemical Journal","volume":"42 1","pages":""},"PeriodicalIF":4.1,"publicationDate":"2025-05-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143945231","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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

Unveiling the role of srbA sRNA in biofilm formation by regulating algU, mucA, rhlA, and rsmA in Pseudomonas aeruginosa. 揭示srbA sRNA在铜绿假单胞菌中通过调节algU、mucA、rhlA和rsmA在生物膜形成中的作用。

IF 4.1 3区生物学

Biochemical Journal Pub Date : 2025-05-07 DOI: 10.1042/bcj20240650

Piyali Saha,Samir Kumar Mukherjee,Sk Tofajjen Hossain

{"title":"Unveiling the role of srbA sRNA in biofilm formation by regulating algU, mucA, rhlA, and rsmA in Pseudomonas aeruginosa.","authors":"Piyali Saha,Samir Kumar Mukherjee,Sk Tofajjen Hossain","doi":"10.1042/bcj20240650","DOIUrl":"https://doi.org/10.1042/bcj20240650","url":null,"abstract":"The survival and increasing antimicrobial resistance of various bacteria, including clinically relevant opportunistic pathogen, Pseudomonas aeruginosa, largely depends on their biofilm architectural strength, that makes a challenge to eradicate it. Small RNAs (sRNAs) have been identified as the key modulators in regulating the expression and function of different transcriptional regulators, and the components of regulatory networks involved in bacterial biofilm formation. This study was focused to identify the regulatory role of the srbA sRNA in controlling biofilm formation in P. aeruginosa. srbA was found to be upregulated in both substratum-attached and colony biofilms compared to planktonic growth conditions. Further analysis revealed that srbA overexpressing strain produced more biofilm, whereas a significant reduction in biofilm formation was noted due to srbA deletion. Interestingly, it was also predicted from the study that srbA might regulate the expression of AlgU/MucA, the sigma and anti-sigma factor, involved in biofilm developmental network. Additionally, srbA showed possible interference on the expression of two other important biofilm regulatory genes, rhlA and rsmA. Overall, this research highlights the critical role of srbA sRNA as a central regulator of biofilm formation, and possibly the pathogenicity of P. aeruginosa. These findings might offer potential avenues for developing targeted therapeutic strategies to mitigate biofilm-related infections caused by P. aeruginosa.","PeriodicalId":8825,"journal":{"name":"Biochemical Journal","volume":"19 1","pages":""},"PeriodicalIF":4.1,"publicationDate":"2025-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143915011","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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