Biochimica et biophysica acta. Molecular cell research最新文献

{"title":"The loss of keratin 77 in murine skin is functionally compensated by keratin 1","authors":"S. Ghorbanalipoor ,&nbsp;T. Hommel ,&nbsp;T. Kolbe ,&nbsp;T. Fröhlich ,&nbsp;B. Wagner ,&nbsp;C. Posch ,&nbsp;M. Dahlhoff","doi":"10.1016/j.bbamcr.2024.119881","DOIUrl":"10.1016/j.bbamcr.2024.119881","url":null,"abstract":"<div><div>Keratins, the intermediate filament-forming proteins of the epithelial cells, are mainly expressed in keratinocytes, preserving the structural integrity and cohesion of the epidermis. There are multiple inherited skin conditions arising from mutations in the encoding genes of specific keratins, highlighting their significance in skin health. Furthermore, the aberrant expression of keratins is evidenced in certain skin diseases, such as psoriasis, atopic dermatitis, and skin cancer. Keratin 77 (KRT77) is a type II keratin with demonstrated expression in human and mouse sweat glands' ducts. Using the CRISPR/Cas9 technique, we generated a <em>Krt77</em>-deficient (<em>Krt77</em>-KO) mouse line to reveal its obscure function in skin biology and homeostasis. KRT77 loss did not result in any fetal lethality or detrimental impact on the development of the skin and its appendages. However, we identified a substantially increased expression of KRT1 in the skin of the <em>Krt77</em>-KO mouse line in comparison with control littermates at both mRNA and protein levels using RT-qPCR and western blot analyses, respectively. Based on these findings, we concluded that the absence of KRT77 in the murine skin leads to upregulation of KRT1, an alternative epidermal type II keratin within the same subfamily as KRT77, which rescues the lack of KRT77.</div></div>","PeriodicalId":8754,"journal":{"name":"Biochimica et biophysica acta. Molecular cell research","volume":"1872 2","pages":"Article 119881"},"PeriodicalIF":4.6,"publicationDate":"2024-11-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142723916","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Ubiquitin-specific peptidase 11 selectively interacts with and deubiquitination-dependently stabilizes diacylglycerol kinase δ to maintain cellular glucose uptake","authors":"Masayuki Ebina ,&nbsp;Yuri Miura ,&nbsp;Fumio Sakane","doi":"10.1016/j.bbamcr.2024.119883","DOIUrl":"10.1016/j.bbamcr.2024.119883","url":null,"abstract":"<div><div>Diacylglycerol kinase δ (DGKδ) phosphorylates diacylglycerol and converts it into phosphatidic acid. DGKδ contributes to glucose uptake as one of its cellular functions. However, detail mechanisms underlying the regulation of DGKδ protein stability remain unelucidated. Herein, we identified ubiquitin-specific peptidase 11 (USP11) in the DGKδ protein complex by DGKδ-interactome analysis. By mapping analysis, we clarified that a wider region of USP11, including the catalytic domain 1 region, and both the C1 domains and catalytic subdomain-a of DGKδ mainly contributed to their association. Cellular dysfunction of USP11 by mitoxiantrone (a USP11-specific inhibitor) or siRNA knockdown markedly decreased DGKδ protein levels. Additionally, we found that DGKδ ubiquitination was increased by USP11 dysfunction, and cumulative ubiquitination was reduced by rescue manipulation. Functionally, USP11 dysfunction reduced cellular glucose uptake. Altogether, our findings provide the first evidence that USP11 deubiquitination-dependently stabilizes DGKδ to maintain cellular glucose uptake.</div></div>","PeriodicalId":8754,"journal":{"name":"Biochimica et biophysica acta. Molecular cell research","volume":"1872 2","pages":"Article 119883"},"PeriodicalIF":4.6,"publicationDate":"2024-11-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142738280","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"ELAVL1 governs breast cancer malignancy by regulating cell stemness","authors":"Long Chen ,&nbsp;Menglu Zhao ,&nbsp;Linjing Liu ,&nbsp;Tan Wang ,&nbsp;Xue Gong ,&nbsp;Jun Zhang","doi":"10.1016/j.bbamcr.2024.119880","DOIUrl":"10.1016/j.bbamcr.2024.119880","url":null,"abstract":"<div><div>Despite advances in understanding breast cancer (BC) molecular subtypes, the mechanisms underlying its grade of malignancy remain unclear. Our study reveals that low expression of the RNA-binding protein ELAVL1 is linked to higher-grade malignancy and poorer prognosis in malignant BC subtypes. Notably, knockdown of ELAVL1 increased the expression of key stem cell markers (CD44, SOX2, OCT4, KLF4, and NANOG) and enhanced tumorsphere formation. These findings offer new insights into BC malignancy and suggest potential improvements in prognostic assessment and treatment strategies for better patient outcomes.</div></div>","PeriodicalId":8754,"journal":{"name":"Biochimica et biophysica acta. Molecular cell research","volume":"1872 2","pages":"Article 119880"},"PeriodicalIF":4.6,"publicationDate":"2024-11-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142698202","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The association of ABC proteins with multidrug resistance in cancer","authors":"Andrezza Viviany Lourenço Marques ,&nbsp;Bruna Estelita Ruginsk ,&nbsp;Larissa de Oliveira Prado,&nbsp;Diogo Eugênio de Lima,&nbsp;Isabelle Watanabe Daniel,&nbsp;Vivian Rotuno Moure,&nbsp;Glaucio Valdameri","doi":"10.1016/j.bbamcr.2024.119878","DOIUrl":"10.1016/j.bbamcr.2024.119878","url":null,"abstract":"<div><div>Multidrug resistance (MDR) poses one of the primary challenges for cancer treatment, especially in cases of metastatic disease. Various mechanisms contribute to MDR, including the overexpression of ATP-binding cassette (ABC) proteins. In this context, we reviewed the literature to establish a correlation between the overexpression of ABC proteins and MDR in cancer, considering both <em>in vitro</em> and clinical studies. Initially, we presented an overview of the seven subfamilies of ABC proteins, along with the subcellular localization of each protein. Subsequently, we identified a panel of 20 ABC proteins (ABCA1–3, ABCA7, ABCB1–2, ABCB4–6, ABCC1–5, ABCC10–11, ABCE1, ABCF2, ABCG1, and ABCG2) associated with MDR. We also emphasize the significance of drug sequestration by certain ABC proteins into intracellular compartments. Among the anticancer drugs linked to MDR, 29 were definitively identified as substrates for at least one of the three most crucial ABC transporters: ABCB1, ABCC1, and ABCG2. We further discussed that the most commonly used drugs in standard regimens for mainly breast cancer, lung cancer, and acute lymphoblastic leukemia could be subject to MDR mediated by ABC transporters. Collectively, these insights will aid in conducting new studies aimed at a deeper understanding of the clinical MDR mediated by ABC proteins and in designing more effective pharmacological treatments to enhance the objective response rate in cancer patients.</div></div>","PeriodicalId":8754,"journal":{"name":"Biochimica et biophysica acta. Molecular cell research","volume":"1872 2","pages":"Article 119878"},"PeriodicalIF":4.6,"publicationDate":"2024-11-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142685839","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Targeting SphK1/S1PR3 axis ameliorates sepsis-induced multiple organ injury via orchestration of macrophage polarization and glycolysis","authors":"Dan Wang ,&nbsp;Xinwen Bi ,&nbsp;Le Zhao ,&nbsp;Shijian Xiang ,&nbsp;Wenjie Xi ,&nbsp;Shushu Yang ,&nbsp;Weijie Wu ,&nbsp;Tufeng Chen ,&nbsp;Lei Zheng ,&nbsp;Xinjin Chi ,&nbsp;Yang Kang","doi":"10.1016/j.bbamcr.2024.119877","DOIUrl":"10.1016/j.bbamcr.2024.119877","url":null,"abstract":"<div><div>Sepsis is a heterogeneous and imprecise disorder characterized by aberrant response to infection which has been accredited for detrimental impact on immune homeostasis. Recently, macrophage metabolism has been recognized as attractive targets to develop novel immunomodulatory therapy for sepsis research. However, the fine-tuning regulators dictating macrophage functions and the specific mechanisms underlying macrophage metabolic reprogramming remain largely obscure. Sphingosine-1-phosphate (S1P), a metabolic mediator of sphingolipid catabolism, predominantly formed through sphingosine kinase 1 (SphK1) catalyzing, mediates inflammation in sepsis by binding to S1P receptor 3 (S1PR3) expressed in macrophages. Here we demonstrate that SphK1/S1PR3 axis was upregulated in lipopolysaccharide (LPS)-induced macrophages and septic mice lungs, cascading the activation of proglycolytic signaling such as HIF-1α, HK2 and PFKFB3. Targeted inhibition of Sphk1 by PF-543 effectively abrogated upregulated SphK1/S1PR3 axis <em>in vitro</em> and <em>in vivo</em>. In addition, PF-543 significantly suppressed sepsis-related inflammation and multi-organ injury <em>in vivo</em>. Furthermore, PF-543 not only blunted key glycolytic enzymes HIF-1α, HK2, and PFKFB3 in LPS-treated macrophages but also inhibited HK2 and PFKFB3 in septic mice. Silencing or inhibiting SphK1 tempered pro-inflammatory M1 macrophages while boosted anti-inflammatory M2 macrophages. Intriguingly, S1PR3 knockdown proficiently dampened glycolysis-associated markers, retrieved LPS-modulated M1/M2 polarization and attenuated NF-κB p65 activation. In conclusion, our study provides the first evidence that PF-543 orchestrates proportional imbalance of macrophage polarization and the Warburg effect in a SphK1/S1PR3 dependent manner during sepsis, mitigating both hyperinflammation and multi-organ failure, adding a novel puzzle piece to pharmacologically exploitable therapy for sepsis.</div></div>","PeriodicalId":8754,"journal":{"name":"Biochimica et biophysica acta. Molecular cell research","volume":"1872 1","pages":"Article 119877"},"PeriodicalIF":4.6,"publicationDate":"2024-11-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142643826","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Iron‑sulfur cluster biogenesis and function in Apicomplexa parasites","authors":"Eléa A. Renaud,&nbsp;Ambre J.M. Maupin,&nbsp;Sébastien Besteiro","doi":"10.1016/j.bbamcr.2024.119876","DOIUrl":"10.1016/j.bbamcr.2024.119876","url":null,"abstract":"<div><div>Iron‑sulfur cluster are ubiquitous and ancient protein cofactors that support a wide array of essential cellular functions. In eukaryotes, their assembly requires specific and dedicated machineries in each subcellular compartment. Apicomplexans are parasitic protists that are collectively responsible for a significant burden on the health of humans and other animals, and most of them harbor two organelles of endosymbiotic origin: a mitochondrion, and a plastid of high metabolic importance called the apicoplast. Consequently, apicomplexan parasites have distinct iron‑sulfur cluster assembly machineries located to their endosymbiotic organelles, as well as a cytosolic pathway. Recent findings have not only shown the importance of iron‑sulfur cluster assembly for the fitness of these parasites, but also highlighted parasite-specific features that may be promising for the development of targeted anti-parasitic strategies.</div></div>","PeriodicalId":8754,"journal":{"name":"Biochimica et biophysica acta. Molecular cell research","volume":"1872 1","pages":"Article 119876"},"PeriodicalIF":4.6,"publicationDate":"2024-11-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142638316","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Impaired insulin signaling and diet-induced type 3 diabetes pathophysiology increase amyloid β expression in the Drosophila model of Alzheimer's disease","authors":"Khushboo Sharma ,&nbsp;Pooja Rai ,&nbsp;Madhu G. Tapadia","doi":"10.1016/j.bbamcr.2024.119875","DOIUrl":"10.1016/j.bbamcr.2024.119875","url":null,"abstract":"<div><div>Compelling evidence has strongly linked unregulated sugar levels to developing Alzheimer's disease, suggesting Alzheimer's to be ‘diabetes of the brain or ‘type 3 diabetes. Insulin resistance contributes to the pathogenesis of Alzheimer's disease due to uncontrolled and unchecked blood glucose, though the interrelatedness between Alzheimer's disease and type 2 diabetes is debatable. Here we describe the consequences of inducing type 3 diabetes by feeding <em>Drosophila</em> on a high sucrose diet, which effectively mimics the pathophysiology of diabetes. A high sucrose diet increases glycogen and lipid accumulation. Inducing type 3 diabetes worsened neurodegeneration and accelerated disease progression in <em>Drosophila</em> expressing the Alzheimer's Familial Arctic mutation. High sucrose milieu also negatively affected locomotor ability and reduced the lifespan in the Alzheimer's disease model of <em>Drosophila</em>. The results showed that creating diabetic conditions by using insulin receptor (InR) knockdown in the eyes of <em>Drosophila</em> led to a degenerative phenotype, indicating a genetic interaction between the insulin signaling pathway and Alzheimer's disease. The expression of PERK reflects disruption in the endoplasmic reticulum homeostasis due to amyloid-β (Aβ) under a high sucrose diet. These observations demonstrated an association between type 3 diabetes and Alzheimer's disease, and that a high sucrose environment has a degenerating effect on Alzheimer's disease condition.</div></div>","PeriodicalId":8754,"journal":{"name":"Biochimica et biophysica acta. Molecular cell research","volume":"1872 1","pages":"Article 119875"},"PeriodicalIF":4.6,"publicationDate":"2024-11-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142614043","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Interplay of force and local mechanisms in axonal plasticity and beyond","authors":"A. Falconieri","doi":"10.1016/j.bbamcr.2024.119874","DOIUrl":"10.1016/j.bbamcr.2024.119874","url":null,"abstract":"<div><div>The interactions between mechanical forces and neuronal dynamics have long intrigued researchers. Several studies revealed that force plays a pivotal role in shaping axonal outgrowth. However, the molecular mechanisms underpinning force-driven axonal plasticity remain not completely elucidated. This review explores the relationship between force and axonal plasticity, with a focus on local mechanisms, including local translation and axonal transport, and the emerging concept of force-driven cross-talk, a dialogue in which local dynamics are tightly regulated. Recent experimental evidence suggests that microtubules may serve as key mediators of this cross-talk, orchestrating the coordination between local mechanisms and facilitating mass addition.</div></div>","PeriodicalId":8754,"journal":{"name":"Biochimica et biophysica acta. Molecular cell research","volume":"1872 1","pages":"Article 119874"},"PeriodicalIF":4.6,"publicationDate":"2024-11-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142614045","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Oncogenic KRAS mutations modulate BAX-mediated cell death","authors":"Anabela Ferreira ,&nbsp;Stéphen Manon ,&nbsp;Akandé Rouchidane Eyitayo ,&nbsp;Susana R. Chaves ,&nbsp;Manuela Côrte-Real ,&nbsp;Ana Preto ,&nbsp;Maria João Sousa","doi":"10.1016/j.bbamcr.2024.119872","DOIUrl":"10.1016/j.bbamcr.2024.119872","url":null,"abstract":"<div><div>Kirsten rat sarcoma viral oncogene homolog (KRAS) belongs to the GTPase RAS superfamily, which regulates several cell-signaling pathways involved in the control of important cellular functions, including apoptosis. Oncogenic mutations in KRAS are considered the most common gain-of-function mutations, affecting 30–50 % of colorectal cancer (CRC) patients. While RAS proteins usually play an anti-apoptotic role, little is known about the involvement of KRAS mutations in apoptosis regulation. Here, we aimed to elucidate the role of mutated human KRAS in the regulation of BAX, a key pro-apoptotic member of the Bcl-2 family. For this purpose, we took advantage of the simpler yeast model <em>Saccharomyces cerevisiae</em>, using cells deficient in the main yeast RAS isoform (<em>ras2</em>Δ) co-expressing wild-type KRAS (KRAS^WT) or the most frequent KRAS mutations found in CRC - KRAS^G12D, KRAS^G12V or KRAS^G13D, along with human BAX. We show that, in comparison with KRAS^WT, KRAS mutants confer resistance to BAX-induced death and cytochrome <em>c</em> (cyt <em>c</em>) release. The modulation of BAX by KRAS isoforms seems to result from a direct interaction between these proteins, as they co-localize at the mitochondria and there is evidence they may physically interact. We further show that acetic acid significantly increased cell death in cells expressing BAX and co-expressing oncogenic KRAS mutants, but not KRAS^WT. This suggests a potential mechanism explaining the increased sensitivity of CRC cells harboring a KRAS-activated pathway to acetate. These findings contribute to a clearer understanding of how KRAS regulate BAX function, a relevant aspect in tumor progression.</div></div>","PeriodicalId":8754,"journal":{"name":"Biochimica et biophysica acta. Molecular cell research","volume":"1872 1","pages":"Article 119872"},"PeriodicalIF":4.6,"publicationDate":"2024-11-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142614049","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Metformin induces apoptosis in TRAIL-resistant colorectal cancer cells","authors":"Da Eun Lee ,&nbsp;Hae Min Lee ,&nbsp;Yunhyeok Jun ,&nbsp;Soo Young Choi ,&nbsp;Su Jin Lee ,&nbsp;Oh-Shin Kwon","doi":"10.1016/j.bbamcr.2024.119873","DOIUrl":"10.1016/j.bbamcr.2024.119873","url":null,"abstract":"<div><div>Resistance to chemotherapy drugs, which commonly occurs during the treatment of colorectal cancer (CRC), can lead to tumor recurrence and metastasis, so combinational treatment strategies according to the cancer cell type are urgently needed to overcome drug resistance and increase therapeutic efficiency. To this end, the tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) is a promising anticancer strategy. Some CRC cell lines such as SW620 have low sensitivity to TRAIL, so additional sensitizers are required to make the strategy effective. Therefore, we focused on the apoptotic effect of combinational metformin and TRAIL treatment on TRAIL-resistant SW620 cells. Treatment with TRAIL alone did not induce apoptosis whereas combined treatment with metformin and TRAIL significantly increased it. TRAIL activated caspases through an extrinsic pathway but increased resistance to apoptosis through the protein kinase B or AKT (PKB/AKT)/mammalian target of rapamycin (mTOR) pathway. On the other hand, metformin reduced the inhibitory effect of X-linked inhibitor of apoptosis (XIAP) by blocking the AKT and nuclear factor kappa B (NF-κB) pathways and activated CCAAT-enhancer-binding protein homologous protein (CHOP) via endoplasmic reticulum (ER) stress but without inducing apoptosis. In addition, metformin induced cell-cycle arrest, thereby blocking cell proliferation and growth. These results were also confirmed through an in vivo mouse xenograft CRC model, in which combined treatment with metformin and TRAIL induced tumor cell death, thus demonstrating the anticancer effect of their coadministration. Therefore, cotreatment of metformin and TRAIL could be an effective anticancer treatment strategy for TRAIL-resistant CRC.</div></div>","PeriodicalId":8754,"journal":{"name":"Biochimica et biophysica acta. Molecular cell research","volume":"1872 1","pages":"Article 119873"},"PeriodicalIF":4.6,"publicationDate":"2024-11-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142582009","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}