Advances in biological regulation最新文献

Insights into phosphatidic acid phosphatase and its potential role as a therapeutic target.

Advances in biological regulation Pub Date : 2025-01-03 DOI: 10.1016/j.jbior.2025.101074

George M Carman, Geordan J Stukey, Ruta Jog, Gil-Soo Han

引用次数: 0

Molecular basis of JAK kinase regulation guiding therapeutic approaches: Evaluating the JAK3 pseudokinase domain as a drug target.

Advances in biological regulation Pub Date : 2024-12-24 DOI: 10.1016/j.jbior.2024.101072

Anniina Virtanen, Vivian Kettunen, Kirsikka Musta, Veera Räkköläinen, Stefan Knapp, Teemu Haikarainen, Olli Silvennoinen

{"title":"Molecular basis of JAK kinase regulation guiding therapeutic approaches: Evaluating the JAK3 pseudokinase domain as a drug target.","authors":"Anniina Virtanen, Vivian Kettunen, Kirsikka Musta, Veera Räkköläinen, Stefan Knapp, Teemu Haikarainen, Olli Silvennoinen","doi":"10.1016/j.jbior.2024.101072","DOIUrl":"https://doi.org/10.1016/j.jbior.2024.101072","url":null,"abstract":"Janus kinases (JAK1-3, TYK2) are critical mediators of cytokine signaling and their role in hematological and inflammatory and autoimmune diseases has sparked widespread interest in their therapeutic targeting. JAKs have unique tandem kinase structure consisting of an active tyrosine kinase domain adjacent to a pseudokinase domain that is a hotspot for pathogenic mutations. The development of JAK inhibitors has focused on the active kinase domain and the developed drugs have demonstrated good clinical efficacy but due to off-target inhibition cause also side-effects and carry a black box warning limiting their use. Our understanding of the regulatory function of the pseudokinase domain in physiological and pathological signaling has improved substantially. The pseudokinase domain maintains the inactive state of JAKs in the absence of cytokine stimulation but it has also a key role in physiological and mutation-driven activation process. Furthermore, the pseudokinase domain has favourable structural characteristics for selective targeting of cytokine signaling, such as unique mode of ATP-binding, and the first pseudokinase targeting inhibitor for TYK2 has been approved for clinical use. Here we describe the recent functional and structural knowledge of JAK signaling and their therapeutic targeting, and present data evaluating the druggability of the JAK3 pseudokinase domain.","PeriodicalId":7214,"journal":{"name":"Advances in biological regulation","volume":" ","pages":"101072"},"PeriodicalIF":0.0,"publicationDate":"2024-12-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142926294","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Tissue specific roles of fatty acid oxidation.

Advances in biological regulation Pub Date : 2024-12-05 DOI: 10.1016/j.jbior.2024.101070

Danielle M Smith, Joseph Choi, Michael J Wolfgang

{"title":"Tissue specific roles of fatty acid oxidation.","authors":"Danielle M Smith, Joseph Choi, Michael J Wolfgang","doi":"10.1016/j.jbior.2024.101070","DOIUrl":"https://doi.org/10.1016/j.jbior.2024.101070","url":null,"abstract":"Mitochondrial long chain fatty acid β-oxidation is a critical central carbon catabolic process. The importance of fatty acid oxidation is made evident by the life-threatening disease associated with diverse inborn errors in the pathway. While inborn errors show multisystemic requirements for fatty acid oxidation, it is not clear from the clinical presentation of these enzyme deficiencies what the tissue specific roles of the pathway are compared to secondary systemic effects. To understand the cell or tissue specific contributions of fatty acid oxidation to systemic physiology, conditional knockouts in mice have been employed to determine the requirements of fatty acid oxidation in disparate cell types. This has produced a host of surprising results that sometimes run counter to the canonical view of this metabolic pathway. The rigor of conditional knockouts has also provided clarity over previous research utilizing cell lines in vitro or small molecule inhibitors with dubious specificity. Here we will summarize current research using mouse models of Carnitine Palmitoyltransferases to determine the tissue specific roles and requirements of long chain mitochondrial fatty acid β-oxidation.","PeriodicalId":7214,"journal":{"name":"Advances in biological regulation","volume":" ","pages":"101070"},"PeriodicalIF":0.0,"publicationDate":"2024-12-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142821765","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Signaling pathways and bone marrow microenvironment in myelodysplastic neoplasms.

Advances in biological regulation Pub Date : 2024-12-04 DOI: 10.1016/j.jbior.2024.101071

Eleonora Ceneri, Alessia De Stefano, Irene Casalin, Carlo Finelli, Antonio Curti, Stefania Paolini, Sarah Parisi, Federica Ardizzoia, Gianluca Cristiano, Jaqueline Boultwood, James A McCubrey, Pann-Ghill Suh, Giulia Ramazzotti, Roberta Fiume, Stefano Ratti, Lucia Manzoli, Lucio Cocco, Matilde Y Follo

{"title":"Signaling pathways and bone marrow microenvironment in myelodysplastic neoplasms.","authors":"Eleonora Ceneri, Alessia De Stefano, Irene Casalin, Carlo Finelli, Antonio Curti, Stefania Paolini, Sarah Parisi, Federica Ardizzoia, Gianluca Cristiano, Jaqueline Boultwood, James A McCubrey, Pann-Ghill Suh, Giulia Ramazzotti, Roberta Fiume, Stefano Ratti, Lucia Manzoli, Lucio Cocco, Matilde Y Follo","doi":"10.1016/j.jbior.2024.101071","DOIUrl":"https://doi.org/10.1016/j.jbior.2024.101071","url":null,"abstract":"Key signaling pathways within the Bone Marrow Microenvironment (BMM), such as Notch, Phosphoinositide-Specific Phospholipase C (PI-PLCs), Transforming Growth Factor β (TGF-β), and Nuclear Factor Kappa B (NF-κB), play a vital role in the progression of Myelodysplastic Neoplasms (MDS). Among the various BMM cell types, Mesenchymal Stromal Cells (MSCs) are particularly central to these pathways. While these signaling routes can independently affect both MSCs and Hematopoietic Stem Cells (HSCs), they most importantly alter the dynamics of their interactions, leading to abnormal changes in survival, differentiation, and quiescence. Notch and PI-PLC signaling facilitate intercellular communication, TGF-β promotes quiescence and suppresses hematopoiesis, and NF-κB-driven inflammatory responses foster an environment detrimental to normal hematopoiesis. This review highlights the role of these pathways within the MDS microenvironment, driving the development and progression of the disease and paving the way for new possible therapeutic strategies.","PeriodicalId":7214,"journal":{"name":"Advances in biological regulation","volume":" ","pages":"101071"},"PeriodicalIF":0.0,"publicationDate":"2024-12-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142794342","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Cellular responses to low nutrient conditions via activation of lysophosphatidic acid (LPA) receptor signaling in gastric cancer cells

Advances in biological regulation Pub Date : 2024-11-30 DOI: 10.1016/j.jbior.2024.101068

Narumi Yashiro, Miwa Takai, Mao Yamamoto, Yuka Kusumoto, Shion Nagano, Anri Taniguchi, Moemi Tamura, Toshifumi Tsujiuchi

{"title":"Cellular responses to low nutrient conditions via activation of lysophosphatidic acid (LPA) receptor signaling in gastric cancer cells","authors":"Narumi Yashiro, Miwa Takai, Mao Yamamoto, Yuka Kusumoto, Shion Nagano, Anri Taniguchi, Moemi Tamura, Toshifumi Tsujiuchi","doi":"10.1016/j.jbior.2024.101068","DOIUrl":"10.1016/j.jbior.2024.101068","url":null,"abstract":"<div><div>In the center of the solid tumor, abnormal vascular architecture impedes sufficient blood supply, leading to continuous hypoxia and nutrient deprivation for the tumor cells. Lysophosphatidic acid (LPA) receptor signaling is known to drive a range of malignant behaviors in cancer cells. This study aimed to explore the impact of LPA receptors on cellular functions in gastric cancer AGS cells cultured under low nutrient conditions. When AGS cells were cultured in media containing low glucose (2000 mg/L), low glutamine (1 mM), or low amino acids (50 % content), LPA receptor expression levels were significantly altered. The growth activity of AGS cells cultured in low glucose- and low amino acid-containing media was suppressed by LPA. Conversely, LPA increased the growth activity of AGS cells cultured in low glutamine-containing media. AGS cell motility increased under low glucose and low glutamine conditions, while low amino acid conditions decreased cell motility. Additionally, the viability of AGS cells in response to cisplatin (CDDP) was enhanced under low glucose, low glutamine, and low amino acid conditions. The motility and viability of AGS cells in response to CDDP were significantly increased by AM966 (LPA1 antagonist), GRI-977143 (LPA2 agonist) and (2S)-OMPT (LPA3 agonist). These results suggest that LPA receptor signaling is significantly implicated in regulating malignant properties in AGS cells under low nutrient conditions.</div></div>","PeriodicalId":7214,"journal":{"name":"Advances in biological regulation","volume":"96 ","pages":"Article 101068"},"PeriodicalIF":0.0,"publicationDate":"2024-11-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142759699","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

The perinucleolar compartment and the oncogenic super-enhancers are part of the same phase-separated structure filled with phosphatidylinositol 4,5bisphosphate and long noncoding RNA HANR.

Advances in biological regulation Pub Date : 2024-11-30 DOI: 10.1016/j.jbior.2024.101069

Ana Miladinović, Ludovica Antiga, Tomáš Venit, Andrea Bayona-Hernandez, Jakub Červenka, Rajendra Kumar Labala, Michal Kolář, Enrique Castaño, Martin Sztacho, Pavel Hozak

{"title":"The perinucleolar compartment and the oncogenic super-enhancers are part of the same phase-separated structure filled with phosphatidylinositol 4,5bisphosphate and long noncoding RNA HANR.","authors":"Ana Miladinović, Ludovica Antiga, Tomáš Venit, Andrea Bayona-Hernandez, Jakub Červenka, Rajendra Kumar Labala, Michal Kolář, Enrique Castaño, Martin Sztacho, Pavel Hozak","doi":"10.1016/j.jbior.2024.101069","DOIUrl":"https://doi.org/10.1016/j.jbior.2024.101069","url":null,"abstract":"The liquid-liquid phase separation in the cell nucleus regulates various processes such as gene regulation and transcription control, chromatin organization, and DNA repair. A plethora of proteins and RNAs contribute to the formation of biomolecular condensates and recently, several nuclear phosphoinositides were shown to be a part of these membrane-less complexes within the nucleus as well. Here we lipid-interacting RNA sequencing (LIPRNAseq) and confocal microscopy to uncover the RNA-binding capacity and localization of phosphatidylinositol 4,5 bisphosphate (PIP2). We discovered the consensus PIP2-binding AU-rich RNA motif and identified long non-coding RNA HANR (lncHANR) to colocalize with PIP2 in the proximity to the nucleolus in the perinucleolar compartment (PNC). Colocalization studies with different nuclear markers reveal that PIP2-HANR presence in the PNC correlates with oncogenic super-enhancers, and both PNC and oncogenic enhancers are part of the same structure. As lncHANR, PNC, and oncogenic super-enhancers are associated with cancer cell lines and tumors, we suggest that they can serve as interchangeable prognostic markers. Understanding of the interplay between lipid metabolism, and lncRNAs in subnuclear compartment phase separation can lead to future improvement in treatment strategies and personalized cancer management approaches.","PeriodicalId":7214,"journal":{"name":"Advances in biological regulation","volume":" ","pages":"101069"},"PeriodicalIF":0.0,"publicationDate":"2024-11-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142794309","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

A budding yeast-centric view of oxysterol binding protein family function.

Advances in biological regulation Pub Date : 2024-11-23 DOI: 10.1016/j.jbior.2024.101061

Xiaohan Yu, Carl J Mousley, Vytas A Bankaitis, Prasanna Iyer

{"title":"A budding yeast-centric view of oxysterol binding protein family function.","authors":"Xiaohan Yu, Carl J Mousley, Vytas A Bankaitis, Prasanna Iyer","doi":"10.1016/j.jbior.2024.101061","DOIUrl":"https://doi.org/10.1016/j.jbior.2024.101061","url":null,"abstract":"The Trans Golgi Network (TGN)/endosomal system is a sorting center for cargo brought via the anterograde secretory pathway and the endocytic pathway that internalizes material from the plasma membrane. As many of the cargo that transit this central trafficking hub are components of key homeostatic signaling pathways, TGN/endosomes define a critical signaling hub for cellular growth control. A particularly interesting yet incompletely understood aspect of regulation of TGN/endosome function is control of this system by two families of lipid exchange/lipid transfer proteins. The phosphatidylinositol transfer proteins promote pro-trafficking phosphoinositide (i.e. phosphatidylinositol-4-phosphate) signaling pathways whereas proteins of the oxysterol binding protein family play reciprocal roles in antagonizing those arms of phosphoinositide signaling. The precise mechanisms for how these lipid binding proteins execute their functions remain to be resolved. Moreover, information regarding the coupling of individual members of the oxysterol binding protein family to specific biological activities is particularly sparse. Herein, we review what is being learned regarding functions of the oxysterol binding protein family in the yeast model system. Focus is primarily directed at a discussion of the Kes1/Osh4 protein for which the most information is available.","PeriodicalId":7214,"journal":{"name":"Advances in biological regulation","volume":" ","pages":"101061"},"PeriodicalIF":0.0,"publicationDate":"2024-11-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142754531","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Making PI3K superfamily enzymes run faster. 让 PI3K 超家族酶跑得更快

Advances in biological regulation Pub Date : 2024-11-19 DOI: 10.1016/j.jbior.2024.101060

Grace Q Gong, Madhangopal Anandapadamanaban, Md Saiful Islam, Iain M Hay, Maxime Bourguet, Saulė Špokaitė, Antoine N Dessus, Yohei Ohashi, Olga Perisic, Roger L Williams

{"title":"Making PI3K superfamily enzymes run faster.","authors":"Grace Q Gong, Madhangopal Anandapadamanaban, Md Saiful Islam, Iain M Hay, Maxime Bourguet, Saulė Špokaitė, Antoine N Dessus, Yohei Ohashi, Olga Perisic, Roger L Williams","doi":"10.1016/j.jbior.2024.101060","DOIUrl":"https://doi.org/10.1016/j.jbior.2024.101060","url":null,"abstract":"The phosphoinositide 3-kinase (PI3K) superfamily includes lipid kinases (PI3Ks and type III PI4Ks) and a group of PI3K-like Ser/Thr protein kinases (PIKKs: mTOR, ATM, ATR, DNA-PKcs, SMG1 and TRRAP) that have a conserved C-terminal kinase domain. A common feature of the superfamily is that they have very low basal activity that can be greatly increased by a range of regulatory factors. Activators reconfigure the active site, causing a subtle realignment of the N-lobe of the kinase domain relative to the C-lobe. This realignment brings the ATP-binding loop in the N-lobe closer to the catalytic residues in the C-lobe. In addition, a conserved C-lobe feature known as the PIKK regulatory domain (PRD) also can change conformation, and PI3K activators can alter an analogous PRD-like region. Recent structures have shown that diverse activating influences can trigger these conformational changes, and a helical region clamping onto the kinase domain transmits regulatory interactions to bring about the active site realignment for more efficient catalysis. A recent report of a small-molecule activator of PI3Kα for application in nerve regeneration suggests that flexibility of these regulatory elements might be exploited to develop specific activators of all PI3K superfamily members. These activators could have roles in wound healing, anti-stroke therapy and treating neurodegeneration. We review common structural features of the PI3K superfamily that may make them amenable to activation.","PeriodicalId":7214,"journal":{"name":"Advances in biological regulation","volume":" ","pages":"101060"},"PeriodicalIF":0.0,"publicationDate":"2024-11-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142724465","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Lamins and chromatin join forces. 鞣质和染色质联手

Advances in biological regulation Pub Date : 2024-11-09 DOI: 10.1016/j.jbior.2024.101059

Baihui Wang, Qiang Luo, Ohad Medalia

引用次数: 0

Fructose 1,6-bisphosphatase as a promising target of anticancer treatment. 果糖-1,6-二磷酸酶有望成为抗癌治疗的靶点。

Advances in biological regulation Pub Date : 2024-10-23 DOI: 10.1016/j.jbior.2024.101057

Agnieszka Gizak, Bartosz Budziak, Aleksandra Domaradzka, Łukasz Pietras, Dariusz Rakus

{"title":"Fructose 1,6-bisphosphatase as a promising target of anticancer treatment.","authors":"Agnieszka Gizak, Bartosz Budziak, Aleksandra Domaradzka, Łukasz Pietras, Dariusz Rakus","doi":"10.1016/j.jbior.2024.101057","DOIUrl":"https://doi.org/10.1016/j.jbior.2024.101057","url":null,"abstract":"Fructose 1,6-bisphosphatase (FBP) is a regulatory enzyme of gluconeogenesis that also influences in a non-catalytic manner - via protein-protein interactions - cell cycle-dependent events, mitochondria biogenesis and polarization, synaptic plasticity and even cancer progression. FBP reduces glycolytic capacity of cells via blocking HIF-1α transcriptional activity and modulating NF-κB action, and influences oxidative metabolism by binding to c-MYC. Because FBP limits the energy-producing potential of cells and because a reduction of FBP amounts is observed in cancer cells, FBP is considered to be an anti-oncogenic protein. This is supported by the observation that cancer cells overexpress aldolase A (ALDOA), a pro-oncogenic protein that can bind to FBP and potentially block its anti-oncogenic activity. Interestingly, only the muscle isozyme of FBP (FBP2) interacts strongly with ALDOA, whereas the binding of the liver isozyme (FBP1) to ALDOA is more than an order of magnitude weaker. Here, we briefly review the most important evidence supporting the anti-oncogenic function of FBP and discuss what structural properties of the two FBP isozymes allow FBP2, rather than FBP1, to exert more flexible anticancer functions.","PeriodicalId":7214,"journal":{"name":"Advances in biological regulation","volume":" ","pages":"101057"},"PeriodicalIF":0.0,"publicationDate":"2024-10-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142567265","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0