{"title":"Fluorescence-based techniques for investigating estrogen receptor dynamics.","authors":"Kiseok Han, Gyuho Choi, Tae-Jin Kim","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Understanding estrogen receptor (ER) signaling pathways is crucial for uncovering the mechanisms behind estrogen-related diseases, such as breast cancer, and addressing the effects of environmental estrogenic disruptors. Traditionally, ER signaling involves genomic events, including ligand binding, receptor dimerization, and transcriptional modulation within cellular nuclei. However, recent research have revealed ERs also participate in non-genomic signaling pathways, adding complexity to their functions. Researchers use advanced fluorescence-based techniques, leveraging fluorescent probes (FPb) to study ER dynamics in living cells, such as spatial distribution, expression kinetics, and functional activities. This review systematically examines the application of fluorescent probes in ER signaling research, covering the visualization of ER, ligandreceptor interactions, receptor dimerization, estrogen response elements (EREs)-mediated transcriptional activation, and G-proteincoupled estrogen receptor (GPER) signaling. Our aim is to provide researchers with valuable insights for employing FPb in their explorations of ER signaling. [BMB Reports 2024; 57(11): 472-483].</p>","PeriodicalId":9010,"journal":{"name":"BMB Reports","volume":" ","pages":"472-483"},"PeriodicalIF":2.9,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11608856/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142104037","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}
Minsu Na, Huiram Kang, Nayoung Kim, Areum Jo, Hae-Ock Lee
{"title":"Characterization of an orthotopic mouse transplant model reveals early changes in the tumor microenvironment of lung cancer.","authors":"Minsu Na, Huiram Kang, Nayoung Kim, Areum Jo, Hae-Ock Lee","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>To understand the cellular and molecular dynamics in the early stages of lung cancer, we explored a mouse model of orthotopic tumor transplant created from the Lewis Lung Carcinoma (LLC) cell line. Employing single-cell RNA sequencing, we analyzed the cellular landscape during tumor engraftment, focusing particularly on LLC cells harboring the Kras G12C mutation. This allowed us to identify LLC tumor cells via the detection of mutant Kras transcripts and observe elevated levels of Myc and mesenchymal gene expression. Moreover, our study revealed significant alterations in the lung microenvironment, including the activation of tissue remodeling genes in fibroblasts and the downregulation of MHC class II genes in myeloid subsets. Additionally, T/NK cell subsets displayed more regulatory phenotypes, coupled with reduced proliferation in CD8+ T cells. Collectively, these findings enhance our understanding of lung cancer progression, particularly in a tumor microenvironment with low immunogenicity. [BMB Reports 2024; 57(11): 484-489].</p>","PeriodicalId":9010,"journal":{"name":"BMB Reports","volume":" ","pages":"484-489"},"PeriodicalIF":2.9,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11608852/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141750979","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}
{"title":"Stromal cells and epigenetics: emerging key players of chronic inflammatory skin diseases.","authors":"Jihye Kim, Michael Detmar","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Epigenetic alterations play a crucial role in developmental processes, tissue regeneration, and cellular differentiation. Epigenetic changes are dynamically reversible. Various drugs that target DNA methyltransferases or histone deacetylases have demonstrated their ability to restore normal epigenetic patterns in a number of diseases. While the involvement of epigenetic modifications has been identified in chronic inflammatory diseases, their specific impact on skin inflammation in stromal cells remains unclear. This mini-review explores the role of stromal cells in chronic inflammatory skin diseases, focusing on epigenetic modifications of stromal cells such as fibroblasts, lymphatic, and blood vascular endothelial cells in both healthy and diseased skin. We also provide an overview of recent findings that highlight the contribution of stromal cells, including fibroblasts, to inflammatory and remodeling processes through epigenetic changes in the context of chronic inflammatory conditions. Investigating epigenetic reprogramming of stromal cells might lead to novel strategies for treating chronic inflammatory skin diseases. [BMB Reports 2024; 57(11): 465-471].</p>","PeriodicalId":9010,"journal":{"name":"BMB Reports","volume":" ","pages":"465-471"},"PeriodicalIF":2.9,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11608854/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142104041","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}
Hyeryung Yoon, Chaemyeong Lim, Bo Lyu, Qisheng Song, So-Yon Park, Kiyoon Kang, Sung-Hwan Cho, Nam-Chon Paek
{"title":"Rice CHD3/Mi-2 chromatin remodeling factor RFS regulates vascular development and root formation by modulating the transcription of auxin-related genes NAL1 and OsPIN1.","authors":"Hyeryung Yoon, Chaemyeong Lim, Bo Lyu, Qisheng Song, So-Yon Park, Kiyoon Kang, Sung-Hwan Cho, Nam-Chon Paek","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>The vascular system in plants facilitates long-distance transportation of water and nutrients through the xylem and phloem, while also providing mechanical support for vertical growth. Although many genes that regulate vascular development in rice have been identified, the mechanism by which epigenetic regulators control vascular development remains unclear. This study found that Rolled Fine Striped (RFS), a Chromodomain Helicase DNA-binding 3 (CHD3)/Mi-2 subfamily protein, regulates vascular development in rice by affecting the initiation and development of primordia. The rfs mutant was found to affect auxin-related genes, as revealed by RNA sequencing and reverse transcription-quantitative PCR analysis. The transcript levels of OsPIN1 and NAL1 genes were downregulated in rfs mutant, compared to the wild-type plant. The chromatin immunoprecipitation assays showed lower levels of H3K4me3 in the OsPIN1a and NAL1 genes in rfs mutant. Furthermore, exogenous auxin treatment partially rescued the reduced adventitious root vascular development in rfs mutant. Subsequently, exogenous treatments with auxin or an auxin-transport inhibitor revealed that the expression of OsPIN1a and NAL1 is mainly affected by auxin. These results provide strong evidence that RFS plays an important role in vascular development and root formation through the auxin signaling pathway in rice. [BMB Reports 2024; 57(10): 441-446].</p>","PeriodicalId":9010,"journal":{"name":"BMB Reports","volume":" ","pages":"441-446"},"PeriodicalIF":2.9,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11524826/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141750982","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}
Hyo Jin Park, Su Min Kim, Un Yung Choi, Lark Kyun Kim
{"title":"Multifaceted roles of trained immunity in diverse pathological contexts.","authors":"Hyo Jin Park, Su Min Kim, Un Yung Choi, Lark Kyun Kim","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Trained immunity, an innate immune response characterized by enhanced cellular responsiveness, exhibits a profound memory akin to adaptive immunity. This phenomenon involves intricate metabolic and epigenetic reprogramming triggered by stimuli such as β-glucan and BCG, shaping innate immune memory. Following elucidation of the background on trained immunity, it is important to explore its multifaceted roles in various pathological contexts. In this review, we delve into the specific contributions of trained immunity in the intricate landscape of viral infections, tumorigenesis, and diverse inflammatory diseases, shedding light on its potential as a therapeutic target, and offering comprehensive understanding of its broader immunological implications. [BMB Reports 2024; 57(10): 431-440].</p>","PeriodicalId":9010,"journal":{"name":"BMB Reports","volume":" ","pages":"431-440"},"PeriodicalIF":2.9,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11524827/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141247417","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}
Joon Bum Kim, Hyejin Hyung, Ji-Eun Bae, Soyoung Jang, Na Yeon Park, Doo Sin Jo, Yong Hwan Kim, Dong Kyu Choi, Hong-Yeoul Ryu, Hyun-Shik Lee, Zae Young Ryoo, Dong-Hyung Cho
{"title":"Increased ER stress by depletion of PDIA6 impairs primary ciliogenesis and enhances sensitivity to ferroptosis in kidney cells.","authors":"Joon Bum Kim, Hyejin Hyung, Ji-Eun Bae, Soyoung Jang, Na Yeon Park, Doo Sin Jo, Yong Hwan Kim, Dong Kyu Choi, Hong-Yeoul Ryu, Hyun-Shik Lee, Zae Young Ryoo, Dong-Hyung Cho","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Primary cilia are crucial for cellular balance, serving as sensors for external conditions. Nephronophthisis and related ciliopathies, which are hereditary and degenerative, stem from genetic mutations in cilia-related genes. However, the precise mechanisms of these conditions are still not fully understood. Our research demonstrates that downregulating PDIA6, leading to cilia removal, makes cells more sensitive to ferroptotic death caused by endoplasmic reticulum (ER) stress. The reduction of PDIA6 intensifies the ER stress response, while also impairing the regulation of primary cilia in various cell types. PDIA6 loss worsens ER stress, hastening ferroptotic death in proximal tubule epithelial cells, HK2 cells. Counteracting this ER stress can mitigate PDIA6 depletion effects, restoring both the number and length of cilia. Moreover, preventing ferroptosis corrects the disrupted primary ciliogenesis due to PDIA6 depletion in HK2 cells. Our findings emphasize the role of PDIA6 in primary ciliogenesis, and suggest its absence enhances ER stress and ferroptosis. These insights offer new therapeutic avenues for treating nephronophthisis and similar ciliopathies. [BMB Reports 2024; 57(10): 453-458].</p>","PeriodicalId":9010,"journal":{"name":"BMB Reports","volume":" ","pages":"453-458"},"PeriodicalIF":2.9,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11524824/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141750980","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}
Myoung Hun Kim, Young Joo Jeong, Sang-Hwa Urm, Dae-Hyun Seog
{"title":"The heterotrimeric kinesin-2 family member KIF3A directly binds to disabled-1 (Dab1).","authors":"Myoung Hun Kim, Young Joo Jeong, Sang-Hwa Urm, Dae-Hyun Seog","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>The heterotrimeric molecular motor kinesin-2 is involved in the microtubule-dependent transport of intracellular cargo. It consists of two distinct motor subunits (KIF3A, and KIF3B) and a non-motor subunit, kinesin-associated protein 3 (KAP3). The cargo-binding domain (CBD) at the carboxyl (C)-terminus of KIF3s plays an important role in the interaction with several different binding proteins. To identify the binding proteins for heterotrimeric kinesin-2, we performed a yeast two-hybrid screen and found a new interaction with Disables-1 (Dab1), the intracellular adaptor protein of reelin receptors. Dab1 bound to the CBD of KIF3A, but did not interact with the C-terminal domain of KIF3B, KIF5B, KIF17 or KAP3. The phosphotyrosine binding (PTB) domain-containing region of Dab1 is essential for the interaction with KIF3A. KIF3A interacted with GST-Dab1, and GST-CaMKIIα, but did not interact with GST-apolipoprotein E receptor 2 (ApoER2)-C or with GST alone. When co-expressed in HEK-293T cells, Dab1 co-precipitated with KIF3A, but not with KIF5B. Dab1 and KIF3A were co-localized in cultured cells. We also identified deduced cell surface expression of ApoER2 in KIF3A dominant-negative cells. These results suggest that the KIF3A plays a role in the intracellular trafficking of ApoER2 to the cell surface. [BMB Reports 2024; 57(10): 447-452].</p>","PeriodicalId":9010,"journal":{"name":"BMB Reports","volume":" ","pages":"447-452"},"PeriodicalIF":2.9,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11524828/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141449628","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}
Jae Kook Yang, Junhyung Kim, Young Hyeon Ahn, Sang Ho Bae, Moo-Jun Baek, Sae Hwan Lee, Jong-Seok Moon
{"title":"Inhibition of P2RX7 contributes to cytotoxicity by suppression of glycolysis and AKT activation in human hepatocellular carcinoma.","authors":"Jae Kook Yang, Junhyung Kim, Young Hyeon Ahn, Sang Ho Bae, Moo-Jun Baek, Sae Hwan Lee, Jong-Seok Moon","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Hepatocellular carcinoma (HCC) is the most common form of primary liver cancer. HCC occurs people with chronic liver diseases. The purinergic receptor P2X 7 (P2RX7) is involved in tumor proliferation and growth. Also, P2RX7 is associated with tumor invasion and metastatic dissemination. High glucose utilization is important for the survival of various types of tumors. However, the role of P2RX7 in glucose metabolism and cellular survival of HCC remains unclear. Here, our results show that the gene and protein levels of P2RX7 were elevated in tumor cells of patients with HCC. The pharmacological inhibition of P2RX7 by A-804598, a selective P2RX7 antagonist, and genetic inhibition by P2RX7 knockdown suppressed the glycolytic activity by reduction of hexokinase 2 (HK2), a key enzyme of the glycolysis pathway, in human HCC cells. Also, both A-804598 treatment and P2RX7 knockdown induced cytotoxicity via inhibition of AKT activation which is critical for tumor cell survival in human HCC cells. Moreover, A-804598 treatment and P2RX7 knockdown increased cytotoxicity and caspase-3 activation in human HCC cells. These results suggest that inhibition of P2RX7 contributes to cytotoxicity by suppression of glycolysis and AKT activation in human HCC. [BMB Reports 2024; 57(10): 459-464].</p>","PeriodicalId":9010,"journal":{"name":"BMB Reports","volume":" ","pages":"459-464"},"PeriodicalIF":2.9,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11524825/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142104039","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}
{"title":"Matricellular proteins in immunometabolism and tissue homeostasis.","authors":"Kyoungjun Eun, Ah Young Kim, Seungjin Ryu","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Matricellular proteins are integral non-structural components of the extracellular matrix. They serve as essential modulators of immunometabolism and tissue homeostasis, playing critical roles in physiological and pathological conditions. These extracellular matrix proteins including thrombospondins, osteopontin, tenascins, the secreted protein acidic and rich in cysteine (SPARC) family, the Cyr61, CTGF, NOV (CCN) family, and fibulins have multi-faceted functions in regulating immune cell functions, metabolic pathways, and tissue homeostasis. They are involved in immune-metabolic regulation and influence processes such as insulin signaling, adipogenesis, lipid metabolism, and immune cell function, playing significant roles in metabolic disorders such as obesity and diabetes. Furthermore, their modulation of tissue homeostasis processes including cellular adhesion, differentiation, migration, repair, and regeneration is instrumental for maintaining tissue integrity and function. The importance of these proteins in maintaining physiological equilibrium is underscored by the fact that alterations in their expression or function often coincide with disease manifestation. This review contributes to our growing understanding of these proteins, their mechanisms, and their potential therapeutic applications. [BMB Reports 2024; 57(9): 400-416].</p>","PeriodicalId":9010,"journal":{"name":"BMB Reports","volume":" ","pages":"400-416"},"PeriodicalIF":2.9,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11444987/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141449589","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}
{"title":"Nuclear structures and their emerging roles in cell differentiation and development.","authors":"Hye Ji Cha","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>The nucleus, a highly organized and dynamic organelle, plays a crucial role in regulating cellular processes. During cell differentiation, profound changes occur in gene expression, chromatin organization, and nuclear morphology. This review explores the intricate relationship between nuclear architecture and cellular function, focusing on the roles of the nuclear lamina, nuclear pore complexes (NPCs), sub-nuclear bodies, and the nuclear scaffold. These components collectively maintain nuclear integrity, organize chromatin, and interact with key regulatory factors. The dynamic remodeling of chromatin, its interactions with nuclear structures, and epigenetic modifications work in concert to modulate gene accessibility and ensure precise spatiotemporal control of gene expression. The nuclear lamina stabilizes nuclear shape and is associated with inactive chromatin regions, while NPCs facilitate selective transport. Sub-nuclear bodies contribute to genome organization and gene regulation, often by influencing RNA processing. The nuclear scaffold provides structural support, impacting 3D genome organization, which is crucial for proper gene expression during differentiation. This review underscores the significance of nuclear architecture in regulating gene expression and guiding cell differentiation. Further investigation into nuclear structure and 3D genome organization will deepen our understanding of the mechanisms governing cell fate determination. [BMB Reports 2024; 57(9): 381-387].</p>","PeriodicalId":9010,"journal":{"name":"BMB Reports","volume":" ","pages":"381-387"},"PeriodicalIF":2.9,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11444988/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142104040","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}