Patrick Delattre, Danny Létourneau, Anna Meller, Xavier Roucou, Francois-Michel Boisvert, Pierre Lavigne
{"title":"Solution NMR Structure and NMR-based Molecular Backbone Dynamics of UbKEKS: A Ubiquitin Variant Encoded in the UBB4 Pseudogene with Emerging Specific and New Functions.","authors":"Patrick Delattre, Danny Létourneau, Anna Meller, Xavier Roucou, Francois-Michel Boisvert, Pierre Lavigne","doi":"10.1139/bcb-2025-0166","DOIUrl":"https://doi.org/10.1139/bcb-2025-0166","url":null,"abstract":"<p><p>Recently, proteomics analyses using databases of unannotated ORFs revealed that ubiquitin (Ub) variants can be encoded and expressed from pseudogenes. One such pseudogene, UBBP4, produces UbKEKS, which contains four substitutions (Q2K, K33E, Q49K, N60S) relative to canonical Ub. Unlike Ub, UbKEKS does not promote proteasomal degradation through K48 linkages and instead modifies a distinct set of proteins. To elucidate the structural basis of this divergence, we solved the NMR solution structure of UbKEKS and characterized its backbone dynamics by 15N-relaxation. While UbKEKS retains the overall helix-grip fold, we observed significant rearrangements and amplified motions in residues governing the Ub pincer mode, a conformational switch that determines whether UIMs engage the canonical I44 interface or the α1-β3 edge. Specifically, Q2K and K33E cooperate to enhance motions on both fast (ps-ns) and slow (µs-ms) timescales within α1, the β1-β2 loop, and β5-regions central to pincer mode regulation. In addition, Q49K, adjacent to I44, perturbs UIM recognition and likely interferes with K48 chain formation and binding to the proteasomal receptor S5a. Collectively, our findings identify structural and dynamical determinants that explain UbKEKS's distinct substrate profile and inability to target proteins for degradation.</p>","PeriodicalId":8775,"journal":{"name":"Biochemistry and Cell Biology","volume":" ","pages":""},"PeriodicalIF":2.1,"publicationDate":"2025-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145211451","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}
Anna Meller, Jennifer Raisch, Dominique Lévesque, Etienne Fafard-Couture, Michelle S Scott, Xavier Roucou, Francois-Michel Boisvert
{"title":"The Pseudogene RPS27AP5 Expresses Ubiquitin and Ribosomal Protein Variants with Potential Roles in Ribosome Function.","authors":"Anna Meller, Jennifer Raisch, Dominique Lévesque, Etienne Fafard-Couture, Michelle S Scott, Xavier Roucou, Francois-Michel Boisvert","doi":"10.1139/bcb-2025-0228","DOIUrl":"https://doi.org/10.1139/bcb-2025-0228","url":null,"abstract":"<p><p>Pseudogenes, traditionally considered non-functional gene copies, have garnered attention due to emerging evidence of their transcription and translation. Ubiquitin is canonically expressed from UBA52 and RPS27A genes as fusion proteins, with additional polyubiquitin precursors encoded by UBB and UBC. Several pseudogenes of these loci are annotated as non-functional. Here, we report that the RPS27A pseudogene, RPS27AP5, expresses two proteins: a ubiquitin variant (UbP5) and a ribosomal protein variant (S27aP5). These proteins mature through cleavage and exhibit localization and biochemical characteristics similar to their parental counterparts. S27aP5 integrates into ribosomes, and its overexpression leads to an increased 80S monosome fraction. Using affinity purification and polysome profiling, we show that S27aP5-containing ribosomes exhibit altered mRNA associations. The findings suggest that RPS27A, a processed pseudogene, can give rise to a ribosomal protein variant capable of integrating into monosomes and influencing mRNA association aligns with growing evidence that ribosomes may exhibit functional diversity.</p>","PeriodicalId":8775,"journal":{"name":"Biochemistry and Cell Biology","volume":" ","pages":""},"PeriodicalIF":2.1,"publicationDate":"2025-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145130050","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}
Rong Zhou, Zhibo Yang, Junwen Wang, Chang Wang, Meijunzi Luo, Yi Pan, Pan Huang, Yi-Ning Yan, Di Long, Haizhen Wang
{"title":"Chelerythrine alleviates inflammation and angiogenesis in a mouse rosacea model via suppressing the NF-κB/p38 MAPK/STAT3 pathways.","authors":"Rong Zhou, Zhibo Yang, Junwen Wang, Chang Wang, Meijunzi Luo, Yi Pan, Pan Huang, Yi-Ning Yan, Di Long, Haizhen Wang","doi":"10.1139/bcb-2025-0124","DOIUrl":"https://doi.org/10.1139/bcb-2025-0124","url":null,"abstract":"<p><strong>Introduction: </strong>Rosacea is a chronic inflammatory skin condition marked by excessive M1 macrophage polarization and angiogenesis, resulting in erythema and tissue inflammation. Despite available treatments, many patients experience recurrent flare-ups. This study explores chelerythrine, a bioactive component of Phellodendri Chinensis Cortex, for its therapeutic potential in rosacea through modulation of NF-κB, p38 MAPK and STAT3 signaling, inflammation, and vascular regulation.</p><p><strong>Methods: </strong>Using an LL-37-induced rosacea-like mouse model, THP-1-derived M1 macrophages and HUVECs, chelerythrine's effects on macrophage polarization, cytokine expression, angiogenesis and pathway activation of NF-κB, p38 MAPK and STAT3 were evaluated.</p><p><strong>Results: </strong>Chelerythrine significantly reduced epidermal thickness, inflammatory cell infiltration, and pro-inflammatory markers (TNF-α and IL-1β). It inhibited NF-κB, p38 MAPK and STAT3 activation and decreased M1 polarization markers, shifting towards an anti-inflammatory profile. Furthermore, chelerythrine reduced vascular density and VEGF expression, impairing angiogenesis-related behaviors in HUVECs.</p><p><strong>Conclusions: </strong>These findings suggest that chelerythrine holds promise as a treatment for rosacea by mitigating inflammation and angiogenesis through targeted multiple pathways and macrophage modulation.</p>","PeriodicalId":8775,"journal":{"name":"Biochemistry and Cell Biology","volume":" ","pages":""},"PeriodicalIF":2.1,"publicationDate":"2025-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144999490","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}
{"title":"KREMEN2 promotes the proliferation and the metastasis through activating PI3K/AKT/mTOR signaling pathway in non-small cell lung cancer.","authors":"Shunying Wang, Li Li, Wenming Wang","doi":"10.1139/bcb-2025-0039","DOIUrl":"https://doi.org/10.1139/bcb-2025-0039","url":null,"abstract":"<p><p>Our purpose was to explore the role and regulatory mechanisms of kringle containing transmembrane protein 2 (KREMEN2) in the development and progression of non-small cell lung cancer (NSCLC). KREMEN2 expression levels were higher in NSCLC tissues and cells than in normal tissues and cells. Down-regulation of KREMEN2 by siRNAs suppressed proliferation, migration, invasion and epithelial mesenchymal transition (EMT), and accelerated apoptosis in NSCLC cells. Furthermore, KREMEN2 knockdown repressed PI3K/AKT/mTOR signaling, and KREMEN2 overexpression activated PI3K/AKT/mTOR signaling. Additionally, PI3K activator (740Y-P) treatment or PI3K overexpression reversed the inhibitory function of KREMEN2 knockdown on proliferation and metastasis, as well as the strengthened function of KREMEN2 knockdown on the apoptosis of NSCLC cells. Moreover, KREMEN2 suppressed tumor growth by inhibiting PI3K/AKT/mTOR signaling in mice. The pharmacologic inhibitor of KREMEN2 (genistein) was also demonstrated to suppress tumor growth in mice. In conclusion, our study suggested that KREMEN2 knockdown could repress the proliferative, migratory, and invasive capacity, as well as EMT, while accelerating the apoptotic capacity of NSCLC cells by inhibiting PI3K/AKT/mTOR signaling.</p>","PeriodicalId":8775,"journal":{"name":"Biochemistry and Cell Biology","volume":" ","pages":""},"PeriodicalIF":2.4,"publicationDate":"2025-07-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144607180","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}
{"title":"Targeting PINK1 using phytochemicals: Exploring molecular insights into Parkinson's disease therapeutics.","authors":"Saranya Nallusamy, Selva Babu Selvamani, Chakkarai Sathyaseelan, Divya Selvakumar, Rashmi Panigrahi","doi":"10.1139/bcb-2024-0280","DOIUrl":"https://doi.org/10.1139/bcb-2024-0280","url":null,"abstract":"<p><p>Parkinson's disease (PD) is one of the most commonly affecting neurodegenerative disorder prevalent in our society. The inherited autosomal recessive PD/parkinsonism occurs due to mutations in six genes including the gene for PTEN (phosphatase and tensin homologue)-induced putative kinase1 (PINK1). The pathophysiology and development of disorders associated with the mitochondria occur simultaneously with the dysregulation of PINK1. The activation/regulation of PINK1 through autophagy regulators can reduce Parkinson's disease condition. This study focused on exploring the possibility of 2062 phytochemicals as autophagy regulators. In silico docking and simulation studies are performed to identify their binding with the PINK1. Our studies highlight the phytochemicals like Proanthocyanidin A-6, Withanolide Q and pseudo-ginsenoside F11 that showed higher binding energy and stable interactions during the course of simulation. This study opens avenues for testing these compounds as positive modulators of PINK1 kinase activity using in vitro and in vivo methods and use of these compounds as phytotherapeutic for treatment of PD.</p>","PeriodicalId":8775,"journal":{"name":"Biochemistry and Cell Biology","volume":" ","pages":""},"PeriodicalIF":2.4,"publicationDate":"2025-07-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144582946","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}
Guobin Xie, Ning Wang, Yunhe Huang, Lun Yang, Shanggan Zeng, Jiangbo Jin
{"title":"TRAF7 inhibits proliferation and migration of esophageal squamous cell carcinoma by ubiquitination-mediated degradation of SOX12.","authors":"Guobin Xie, Ning Wang, Yunhe Huang, Lun Yang, Shanggan Zeng, Jiangbo Jin","doi":"10.1139/bcb-2024-0279","DOIUrl":"https://doi.org/10.1139/bcb-2024-0279","url":null,"abstract":"<p><p>Tumor necrosis factor receptor-associated factor 7(TRAF7), a member of the tumor necrosis factor receptor (TNF-R) superfamily, is known as an E3 ubiquitin ligase and has been shown to contribute to the progression of various cancers. However, the function of TRAF7 in esophageal squamous cell carcinoma (ESCC) remains unclear. Here, our findings demonstrate a marked downregulation of TRAF7 protein expression in esophageal squamous cell carcinoma (ESCC) cell lines compared to non-neoplastic esophageal epithelial cells. Overexpression of TRAF7 inhibited cell proliferation and migration of ESCC cells, as well as promoted cell apoptosis and blocked cell cycle at the G2/M phase. In this study, we observed that TRAF7 interacted with the SOX12 protein and promoted ubiquitin-proteasome-mediated degradation of SOX12 via K48-linked ubiquitination in ESCC cells. Rescue experiments further confirmed that TRAF7's inhibitory effects on tumor cell proliferation and migration in ESCC cells partly depended on SOX12. In summary, our research reveals that TRAF7 functions as a tumor suppressor partially by promoting K48-linked ubiquitination-mediated degradation of the SOX12 protein.</p>","PeriodicalId":8775,"journal":{"name":"Biochemistry and Cell Biology","volume":" ","pages":""},"PeriodicalIF":2.4,"publicationDate":"2025-07-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144582947","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}
Marie-Frédérique Gauthier, Giada Ostinelli, Mélissa Pelletier, André Tchernof
{"title":"Origin of dedifferentiated adipocyte-derived cells (DFAT) during ceiling culture in an Adiponectin Cre-Recombinase mouse model.","authors":"Marie-Frédérique Gauthier, Giada Ostinelli, Mélissa Pelletier, André Tchernof","doi":"10.1139/bcb-2024-0140","DOIUrl":"10.1139/bcb-2024-0140","url":null,"abstract":"<p><p>DFAT cells represent an attractive source of stem cells in tissue engineering and in the potential treatment of several clinical conditions. Our objective was to determine whether DFAT cells originate from mature adipocytes and address whether contamination from the stromal vascular fraction (SVF) could be as a source for these cells. A murine adiponectin-creERT;mT/mG model was used with the excision of the cassette induced by tamoxifen injection for the cells expressing adiponectin (adipoq). This model allows distinguishing of mature adipocytes (green fluorescence) from other SVF cell types (red fluorescence) based on the fluorescent protein expressed. Mature adipocytes and SVF cells were isolated from adipose tissues by collagenase digestion. Ceiling cultures were imaged by time-lapse microscopy. Confocal microscopy was used to follow cells over 21 days. Time-lapse microscopy experiments showed liposecretion occurring in mature adipocytes displaying green fluorescence. Confocal imaging allowed the identification of a heterogeneous cell population expressing green but also red fluorescence after 21 days of culture. Asymmetrical division of mature adipocytes was not observed. In conclusion, liposecretion of mature adipocytes is a phenomenon that can be observed in vitro and DFAT cells do originate from mature adipocytes<i>.</i> However, the population of DFAT cells is heterogenous.</p>","PeriodicalId":8775,"journal":{"name":"Biochemistry and Cell Biology","volume":" ","pages":"1-10"},"PeriodicalIF":2.4,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142543388","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}
Xiaoying Li, Shenggui Liu, Siqi Wang, Xinghui Ai, Lin Wei
{"title":"1-Deoxynojirimycin affects high glucose-induced pancreatic beta-cell dysfunction through regulating CEBPA expression and AMPK pathway.","authors":"Xiaoying Li, Shenggui Liu, Siqi Wang, Xinghui Ai, Lin Wei","doi":"10.1139/bcb-2024-0128","DOIUrl":"10.1139/bcb-2024-0128","url":null,"abstract":"<p><p>This study aims to explore the role of 1-deoxynojirimycin (DNJ) in high glucose-induced β-cells and to further explore the molecular mechanism of DNJ effect on β-cells through network pharmacology. In the study, high glucose treatment of mouse INS-1 cells inhibited cell proliferation and insulin secretion, decreased the expression of Bcl-2 protein and Ins1 and Ins2 genes, promoted apoptosis, and increased cleaved caspase-3 and cleaved caspase-9 expression levels as well as intracellular reactive oxygen species production. DNJ treatment significantly restored the dysfunction of INS-1 cells induced by high glucose, and DNJ showed no toxicity to normal INS-1 cells. Silencing CEBPA promoted, while overexpression of CEBPA relieved the dysfunction of pancreatic β-cells induced by high glucose. DNJ treatment partially restored the pancreatic β-cell dysfunction caused by silencing CEBPA. In conclusion, DNJ can inhibit high glucose-induced pancreatic β-cell dysfunction by promoting the expression of CEBPA.</p>","PeriodicalId":8775,"journal":{"name":"Biochemistry and Cell Biology","volume":" ","pages":"1-12"},"PeriodicalIF":2.4,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142638318","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}
{"title":"Establishment of immortalized porcine intramuscular preadipocytes for the study of lipid metabolism.","authors":"Briana Locke, Ray Lu","doi":"10.1139/bcb-2024-0174","DOIUrl":"10.1139/bcb-2024-0174","url":null,"abstract":"<p><p>Intramuscular adipose tissue is associated with an increased risk for the development of metabolic syndrome. A cellular model of adipogenesis in muscular tissues would be an invaluable tool for studying regulatory factors in this important process. Cellular stress can impact the homeostasis of various metabolic pathways, including lipid metabolism. In this study, a porcine intramuscular preadipocyte cell line was established, which displayed mature adipocyte attributes such as lipid accumulation and increased expression of adipogenic gene markers. Since it is well established that endoplasmic reticulum (ER) and Golgi stress impact adipogenesis, we sought to investigate the effects of ER/Golgi stress and an associated protein, CREB3, in this cell line model. We found that this novel model maintains robust adipogenic capabilities, and that ER stress can negatively affect adipogenic markers. Overall, these findings demonstrate the strength of the new cell model for studying adipogenesis, and highlight the impact of ER stress on lipid metabolism.</p>","PeriodicalId":8775,"journal":{"name":"Biochemistry and Cell Biology","volume":" ","pages":"1-11"},"PeriodicalIF":2.4,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143699617","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}
{"title":"Ophiopogonin D protects against cerebral ischemia-reperfusion injury in rats by inhibiting STAT3 phosphorylation.","authors":"Zheng Tang, Chunmei Liu","doi":"10.1139/bcb-2024-0328","DOIUrl":"10.1139/bcb-2024-0328","url":null,"abstract":"<p><p>Our aim is to explore the protective effect of ophiopogonin D (OPD) on cerebral ischemia/reperfusion injury (CIRI) and its relevant molecular mechanisms. OPD effect on brain injury of CIRI rats was evaluated using 2,3,5-triphenyltetrazolium chloride staining, neurological deficit score, brain water content, hematoxylin and eosin staining, Nissl staining, and terminal deoxynucleotidyl transferase-mediated dUTP nick-end labelling staining. Immunofluorescence, immunohistochemistry, qRT-PCR, Western blot, and relative kits were used for detecting inflammatory factors, oxidative stress related factors, and mRNA and protein levels. The Cell Counting Kit-8 assay and flow cytometry were applied for assessing the viability and apoptosis of oxygen-glucose deprivation)/reoxygenation (OGD/R)-induced PC12 cells. OPD ameliorated brain injury via inhibiting neurons apoptosis, oxidative stress, and inflammatory response in cerebral infarction rats. In addition, we found that OPD attenuated the apoptosis, oxidative stress and inflammatory response in OGD/R-induced PC12 cells. Both in CIRI rats and OGD/R-induced PC12 cells, OPD was demonstrated to inhibit signal transducer and activator of transcription 3 (STAT3) phosphorylation. Moreover, Colivelin TFA (a STAT3 activator) reversed OPD effect on the apoptosis, oxidative stress, and inflammatory response in OGD/R-induced PC12 cells. Our findings demonstrated that OPD could protect against CIRI in rats by inhibiting STAT3 phosphorylation.</p>","PeriodicalId":8775,"journal":{"name":"Biochemistry and Cell Biology","volume":" ","pages":"1-13"},"PeriodicalIF":2.4,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144156078","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}