Biochemical and biophysical research communications最新文献_第7页

Ageing drop by drop: Disturbance of the membrane-less organelle biogenesis as an aging hallmark.

IF 2.5 3区生物学

Biochemical and biophysical research communications Pub Date : 2025-01-01 Epub Date: 2024-11-30 DOI: 10.1016/j.bbrc.2024.151088

Baraa M G A Saqr, Nikolay O Kotoyants, Semen V Nesterov, Vladimir D Manuylov, Guy W Dayhoff, Alexander V Fonin, Konstantin K Turoverov, Irina M Kuznetsova, Valentin I Gordeliy, Nikolay S Ilyinsky, Vladimir N Uversky

{"title":"Ageing drop by drop: Disturbance of the membrane-less organelle biogenesis as an aging hallmark.","authors":"Baraa M G A Saqr, Nikolay O Kotoyants, Semen V Nesterov, Vladimir D Manuylov, Guy W Dayhoff, Alexander V Fonin, Konstantin K Turoverov, Irina M Kuznetsova, Valentin I Gordeliy, Nikolay S Ilyinsky, Vladimir N Uversky","doi":"10.1016/j.bbrc.2024.151088","DOIUrl":"10.1016/j.bbrc.2024.151088","url":null,"abstract":"Despite extensive research, the features associated with the aging phenotype are not all-inclusive and need to be updated on a regular basis to incorporate new findings. We propose to include the dysfunction of membrane-less organelle (MLO) as a new aging hallmark. Special scaffold proteins with a high degree of intrinsic disorder drive the formation of MLOs via the liquid-liquid phase separation (LLPS) process. Aberrant behavior of MLOs was shown to be associated with the pathogenesis of many neurodegenerative diseases. In this work, we challenge the aging through bidirectional bioinformatics analysis of human proteins found in Granulome consisting of 7264 protein and Ageome containing 1624 aging-related proteins. The analysis indicates the interconnectivity of MLOs and aging. Approximately 67 % of the Ageome are presented in Granulome thereby constituting the Intersectome that include 1084 proteins showing an enrichment significantly higher than for the random datasets of the same size. Furthermore, for proteins in 10 representative MLOs, we analyzed in detail molecular functions, association with the already known aging hallmarks, and the roles in MLO formation (scaffold, client, or regulator). Cumulatively, our results strengthen the hypothesis that the dysfunction of MLOs can serve as a potent new aging hallmark.","PeriodicalId":8779,"journal":{"name":"Biochemical and biophysical research communications","volume":"742 ","pages":"151088"},"PeriodicalIF":2.5,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142779323","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

High-resolution crystal structure of PD-1 in complex with retifanlimab, the FDA-approved immune checkpoint blocking antibody for treating Merkel cell carcinoma.

IF 2.5 3区生物学

Biochemical and biophysical research communications Pub Date : 2025-01-01 Epub Date: 2024-11-30 DOI: 10.1016/j.bbrc.2024.151106

Seong-Ha Cho, Jeong-Min Park, Eun Ho Lee, Ye Han Song, Yu-Jeong Jang, Seung-Beom Choi, Yong-Seok Heo

{"title":"High-resolution crystal structure of PD-1 in complex with retifanlimab, the FDA-approved immune checkpoint blocking antibody for treating Merkel cell carcinoma.","authors":"Seong-Ha Cho, Jeong-Min Park, Eun Ho Lee, Ye Han Song, Yu-Jeong Jang, Seung-Beom Choi, Yong-Seok Heo","doi":"10.1016/j.bbrc.2024.151106","DOIUrl":"10.1016/j.bbrc.2024.151106","url":null,"abstract":"Retifanlimab is a humanized monoclonal antibody that specifically targets programmed cell death protein 1 (PD-1), an essential immune checkpoint that modulates T-cell immune responses. Several anti-PD-1 antibodies have been market-approved, marking a significant advancement in the treatment of diverse tumor types by restoring the T-cell immune response. Recently, the US FDA approved retifanlimab for treating metastatic or recurrent locally advanced Merkel cell carcinoma. We present the crystal structure of PD-1 in complex with the retifanlimab Fab at a resolution of 1.54 Å to elucidate the structural basis for the mechanism of action of this antibody. This work clarifies the detailed interactions and conformational alterations that occur upon antibody binding. The epitope of retifanlimab partially overlaps with the ligand binding site, and its binding induced unique conformations of the flexible loops within PD-1, including BC, C'D, and FG loops, thereby optimizing interactions with the antibody. A thorough analysis of its interaction with PD-1 and other FDA-approved anti-PD-1 antibodies may provide valuable insights into the rational design of enhanced therapies to regulate immune responses in cancer treatment.","PeriodicalId":8779,"journal":{"name":"Biochemical and biophysical research communications","volume":"742 ","pages":"151106"},"PeriodicalIF":2.5,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142779350","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

Palmitoyl copper peptide and acetyl tyrosine complex enhances melanin production in both A375 and B16 cell lines.

IF 2.5 3区生物学

Biochemical and biophysical research communications Pub Date : 2025-01-01 Epub Date: 2024-11-28 DOI: 10.1016/j.bbrc.2024.151060

Minhua Hong, Yingyue Gui, Jiayao Xu, Xianglong Zhao, Chunyang Jiang, Jian Zhao, Xiujuan Xin, Dan Liu, Xiaolin Tang, Rong Tang, Faliang An

{"title":"Palmitoyl copper peptide and acetyl tyrosine complex enhances melanin production in both A375 and B16 cell lines.","authors":"Minhua Hong, Yingyue Gui, Jiayao Xu, Xianglong Zhao, Chunyang Jiang, Jian Zhao, Xiujuan Xin, Dan Liu, Xiaolin Tang, Rong Tang, Faliang An","doi":"10.1016/j.bbrc.2024.151060","DOIUrl":"10.1016/j.bbrc.2024.151060","url":null,"abstract":"Copper peptide, a low molecular weight peptide composed of glycyl-L-histidyl-l-lysine-copper, possesses anti-aging, anti-inflammatory, and wound healing properties. In this study, we investigated the effects of a combination agent CP-AcT, composed of palmitoyl copper peptide (pal-GHK-Cu) and acetyl tyrosine (N-Acetyl-l-tyrosine), on melanin production in the human malignant melanoma cell line A375 and the mouse melanoma cell line B16. Firstly, the cytotoxicity of CP-AcT at various concentrations (0-8 μg/mL) on HaCat, HFF, A375, and B16 cells was evaluated. Subsequently, the effects of the CP-AcT on tyrosinase activity both extracellular and intracellularly, as well as on melanin production in two melanoma cell lines, were evaluated under conditions that did not compromise cell viability. Additionally, quantitative gene plex (QGP) combined with branched DNA (bDNA) technology was used to analyze the effects of CP-AcT on the expression of melanin-related genes in A375 cells, with a focus on five specific genes. Finally, the effects of the CP-AcT on the expression of three proteins involved in the biosynthesis pathway of melanin: tyrosinase (TYR), dopachrome tautomerase (DCT), and endothelin 3 (EDN3) were analyzed. The results indicate that the complex CP-AcT effectively promotes melanin production in both types of melanoma cells.","PeriodicalId":8779,"journal":{"name":"Biochemical and biophysical research communications","volume":"742 ","pages":"151060"},"PeriodicalIF":2.5,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142779390","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

Nicaraven enhances the cytotoxicity of X-ray irradiation in cancer cells with homologous recombination deficiency. 尼卡文能增强同源重组缺陷癌细胞在 X 射线照射下的细胞毒性。

IF 2.5 3区生物学

Biochemical and biophysical research communications Pub Date : 2025-01-01 Epub Date: 2024-12-05 DOI: 10.1016/j.bbrc.2024.151153

Yuki Yoshino, Kazuko Ichimiya, Keiichi Jingu, Yuhzo Fujita, Natsuko Chiba

{"title":"Nicaraven enhances the cytotoxicity of X-ray irradiation in cancer cells with homologous recombination deficiency.","authors":"Yuki Yoshino, Kazuko Ichimiya, Keiichi Jingu, Yuhzo Fujita, Natsuko Chiba","doi":"10.1016/j.bbrc.2024.151153","DOIUrl":"10.1016/j.bbrc.2024.151153","url":null,"abstract":"Poly (ADP-ribose) polymerase (PARP) is involved in the repair of DNA single-strand breaks. PARP inhibitors are cytotoxic to cancer cells with homologous recombination (HR) deficiency through a synthetic lethality mechanism. Nicaraven is a hydroxyl radical scavenger that has been investigated for the treatment of organ ischemia such as brain infarction. Nicaraven also shows PARP inhibitory and anti-cancer activity in vitro and in vivo. In this study, we investigated the potential synthetic lethality of nicaraven in cells with HR deficiency and whether the PARP inhibitory and radical scavenger activities of nicaraven contributes to its anti-cancer effects, especially in combination with exposure to ionizing radiation. The results showed that nicaraven was cytotoxic against cancer cells after knockdown of the HR factors BRCA1 or RAD51, indicating that nicaraven exerted synthetic lethal effects on cells with HR deficiency. X-ray irradiation-induced DNA double-strand breaks (DSBs) increased at 2 h and were largely repaired after 24 h in control cells, whereas nicaraven significantly increased the amounts of residual DSBs 24 h after X-ray irradiation, especially in HR-deficient cells. Nicaraven treatment enhanced the cytotoxicity of X-ray irradiation in HR-deficient cells, but not that in HR-proficient cells. These data suggest that the combination of nicaraven with X-ray irradiation selectively increases the cytotoxic effects of X-ray irradiation on HR-deficient cancer cells. Thus, nicaraven might be a valuable agent for cancer therapy, particularly in combination with radiotherapy.","PeriodicalId":8779,"journal":{"name":"Biochemical and biophysical research communications","volume":"742 ","pages":"151153"},"PeriodicalIF":2.5,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142821859","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

Tumor-mimetic hydrogel stiffness regulates cancer stemness properties in H-Ras-transformed cancer model cells. 模拟肿瘤的水凝胶硬度可调节 H-Ras 转化的癌症模型细胞的癌症干特性。

IF 2.5 3区生物学

Biochemical and biophysical research communications Pub Date : 2025-01-01 Epub Date: 2024-12-10 DOI: 10.1016/j.bbrc.2024.151163

Yanpeng Sun, Yuheng Nie, Lei Wang, Jian Ping Gong, Shinya Tanaka, Masumi Tsuda

{"title":"Tumor-mimetic hydrogel stiffness regulates cancer stemness properties in H-Ras-transformed cancer model cells.","authors":"Yanpeng Sun, Yuheng Nie, Lei Wang, Jian Ping Gong, Shinya Tanaka, Masumi Tsuda","doi":"10.1016/j.bbrc.2024.151163","DOIUrl":"10.1016/j.bbrc.2024.151163","url":null,"abstract":"Cancer stem cells (CSCs) cause therapy-resistance and recurrence, therefore an establishment of therapeutic approaches targeting CSCs is essential for eradicating cancers; however, a lot of aspects of the mechanisms of CSCs generation remain unclear. We previously demonstrated that human glioblastoma cell lines cultured on double-network (DN) hydrogel were rapidly reprogrammed into CSCs. To elucidate molecular mechanisms underlying CSCs generation, we here focused on the elastic modulus of hydrogels mimicking the stiffness of tumor tissues. Mouse NIH3T3 fibroblasts transformed with representative oncogenes H-Ras and Src were employed as cancer model cells, and cultured on (2-acrylamido-2-methylpropanesulfonic acid) (PAMPS) gel with different elastic modulus. The H-Ras-, but not Src-, transformed NIH3T3 cells induced stem cell properties on the PAMPS gel, particularly with elastic modulus of approximately 10 kPa that mimics general tumor tissues. On the gels, expression levels of stemness markers such as Sox2, Nanog, and Oct4 were increased in the parental and H-Ras-transformed cells. Pull-down assay demonstrated that multiple proteins in H-Ras-transformed cells bound to the PAMPS gels with 9.3 kPa stiffness, and desmoplakin was identified as one of the gel-bound proteins by LC-MS/MS analysis. Among Ca2+ channels functioning as mechanosensors, the expression levels of TRPC and TRPV families were efficiently increased on the gel with approximately 10 kPa, as well as stemness markers. These data suggest that tumor tissues with the stiffness of 10 kPa effectively trigger the signals for generating CSCs through alterations of membrane structures and Ca2+ influx, which will be beneficial for developing novel therapeutic applications targeting CSCs.","PeriodicalId":8779,"journal":{"name":"Biochemical and biophysical research communications","volume":"743 ","pages":"151163"},"PeriodicalIF":2.5,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142823772","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

Quercetin and calorie restriction improve leptin/adiponectin balance through reducing high-fat diet-induced oxidative stress in male BALB/c mice.

IF 2.5 3区生物学

Biochemical and biophysical research communications Pub Date : 2025-01-01 Epub Date: 2024-11-29 DOI: 10.1016/j.bbrc.2024.151073

Arezou Biyabani, Fereshte Ghorbani, Mehdi Koushki, Keivan Nedaei, Mina Hemmati, Nima Mahdei Nasir Mahalleh, Darya Ghadimi

{"title":"Quercetin and calorie restriction improve leptin/adiponectin balance through reducing high-fat diet-induced oxidative stress in male BALB/c mice.","authors":"Arezou Biyabani, Fereshte Ghorbani, Mehdi Koushki, Keivan Nedaei, Mina Hemmati, Nima Mahdei Nasir Mahalleh, Darya Ghadimi","doi":"10.1016/j.bbrc.2024.151073","DOIUrl":"10.1016/j.bbrc.2024.151073","url":null,"abstract":"Throughout the recent decades, obesity has become a serious health problem that raises the risk of several diseases, including cancer, diabetes, hypertension, heart disease, neurological musculoskeletal disorders, and Non-alcoholic fatty liver disease. Some strategies, such as dietary interventions, calorie restriction (CR), and the use of antioxidant compounds, have been proposed to improve quality of life in relation to obesity. The goal of this study was to characterize the effects of CR and quercetin (QUER) on obesity-induced oxidative stress (OS). Thirty 8-week-old male BALB/c mice were divided into 5 groups of six mice each: normal diet, high-fat diet (HFD), HFD + CR, HFD + QUER (15 mg kg-1, IP), and HFD + QUER + CR. CR was applied as two fasting days with an interval of two days in a week. Catalase (CAT), Paraxonase 1 (PON1) and adiponectin (APN) were decreased in the HFD group, while the combination of QUER and CR increased these parameters. Treatment with QUER and CR improved Alanine transaminase and Alkaline Phosphatase enzyme activity and also the amount of leptin and insulin. Moreover, combined QUER and CR also reduced triacylglycerol (TAG), total cholesterol and TAG droplets in hepatocytes. Decreased OS was associated with the higher expression of NAD(P)H Quinone Oxidoreductase 1(NQO1) and reduced hepatic vacuoles in QUER and CR-HFD treated groups. In conclusion, these findings suggest that the combination of QUER and CR might exert protective impacts on obesity through alleviating OS and the regulation of metabolism.","PeriodicalId":8779,"journal":{"name":"Biochemical and biophysical research communications","volume":"742 ","pages":"151073"},"PeriodicalIF":2.5,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142784079","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

Crystal structures of cystathionine β-lyase and cystathionine β-lyase like protein from Bacillus cereus ATCC 14579.

IF 2.5 3区生物学

Biochemical and biophysical research communications Pub Date : 2025-01-01 Epub Date: 2024-12-04 DOI: 10.1016/j.bbrc.2024.151122

Seul Hoo Lee, Hyeonjeong Yu, Jiyeon Hong, Jihye Seok, Kyung-Jin Kim

{"title":"Crystal structures of cystathionine β-lyase and cystathionine β-lyase like protein from Bacillus cereus ATCC 14579.","authors":"Seul Hoo Lee, Hyeonjeong Yu, Jiyeon Hong, Jihye Seok, Kyung-Jin Kim","doi":"10.1016/j.bbrc.2024.151122","DOIUrl":"10.1016/j.bbrc.2024.151122","url":null,"abstract":"Cystathionine β-lyase (CBL) and cystathionine β-lyase-like protein (CBLP) are key PLP-dependent enzymes involved in methionine biosynthesis. In Bacillus cereus ATCC 14579 CBL (BcCBL) and CBLP (BcCBLP) catalyze the conversion of cystathionine to homocysteine and pyruvate. In this study, we found that both BcCBL and BcCBLP effectively catalyze cystathionine cleavage, with BcCBLP exhibiting a higher catalytic efficiency (kcat) and low substrate affinity (Km). We determined their crystal structures in complex with pyridoxal phosphate (PLP). BcCBL, forming a tetramer, aligns with typical CBLs in sulfur amino acid metabolism, while BcCBLP, forming a dimer, resembles the bifunctional MalY enzyme from Escherichia coli, indicating potential additional regulatory roles. These structural and functional insights highlight the distinct roles of BcCBL and BcCBLP in cellular metabolism. This study provides valuable insights into the structural diversity and potential functions of these enzymes, contributing to the broader knowledge of PLP-dependent enzymatic mechanisms.","PeriodicalId":8779,"journal":{"name":"Biochemical and biophysical research communications","volume":"742 ","pages":"151122"},"PeriodicalIF":2.5,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142791056","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

α -lipoic acid supplementation reduces oxidative stress and inflammation in red skeletal muscle of insulin-resistant rats.

IF 2.5 3区生物学

Biochemical and biophysical research communications Pub Date : 2025-01-01 Epub Date: 2024-12-01 DOI: 10.1016/j.bbrc.2024.151107

Patrycja Dajnowicz-Brzezik, Ewa Żebrowska, Mateusz Maciejczyk, Anna Zalewska, Adrian Chabowski

{"title":"α -lipoic acid supplementation reduces oxidative stress and inflammation in red skeletal muscle of insulin-resistant rats.","authors":"Patrycja Dajnowicz-Brzezik, Ewa Żebrowska, Mateusz Maciejczyk, Anna Zalewska, Adrian Chabowski","doi":"10.1016/j.bbrc.2024.151107","DOIUrl":"10.1016/j.bbrc.2024.151107","url":null,"abstract":"α -lipoic acid (ALA) is an eight-carbon saturated fatty acid with strong antioxidant activity. Despite previous reports of ALA's protective properties in treating cardiovascular and metabolic diseases (including insulin resistance and diabetes), little is known about the compound's effects on skeletal muscle metabolism. In particular, the effect of ALA on glycooxidative and nitrosative damage in red muscles during insulin resistance is unknown. This study investigated the therapeutic potential of ALA on the antioxidant barrier as well as oxidative, nitrosative and carbonyl stress in the red skeletal muscle of rats with high-fat diet-induced insulin resistance. Male Wistar cmdb/outbred rats were divided into four equal groups: control diet (CTRL), high fat diet (HFD), CTRL + ALA (30 mg/kg body weight for 4 weeks; intragastrically) and HFD + ALA. Enzymatic and nonenzymatic antioxidant systems, protein and lipid glycoxidation, nitrosative stress, and selected inflammatory/apoptosis parameters were assessed using colorimetric, fluorimetric, and immune-enzymatic methods. ALA lowered body weight and glucose metabolism parameters in insulin-resistant rats. ALA not only strengthened enzymatic antioxidant defense (by increasing superoxide dismutase, catalase and glutathione peroxidase activity) but also stimulated the synthesis of non-enzymatic GSH. ALA supplementation inhibited lipid peroxidation (decreased lipid hydroperoxides and malondialdehyde content) and prevented protein oxidation (by lowering advanced oxidation protein products concentration) in red muscle. ALA's multifactorial actions on muscle tissue also included inhibition of inflammation and apoptosis, requiring further research to elucidate its effects in metabolic diseases.","PeriodicalId":8779,"journal":{"name":"Biochemical and biophysical research communications","volume":"742 ","pages":"151107"},"PeriodicalIF":2.5,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142817100","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

O-GlcNAcylation of progranulin promotes hepatocellular carcinoma proliferation.

IF 2.5 3区生物学

Biochemical and biophysical research communications Pub Date : 2025-01-01 Epub Date: 2024-12-05 DOI: 10.1016/j.bbrc.2024.151150

Yi Liang, Liqiong Chen, Zhuanglin Huang, Yueliang Li, Hanqin Weng, Lianxian Guo

{"title":"O-GlcNAcylation of progranulin promotes hepatocellular carcinoma proliferation.","authors":"Yi Liang, Liqiong Chen, Zhuanglin Huang, Yueliang Li, Hanqin Weng, Lianxian Guo","doi":"10.1016/j.bbrc.2024.151150","DOIUrl":"10.1016/j.bbrc.2024.151150","url":null,"abstract":"Progranulin (PGRN) is overexpressed and implicated in hepatocellular carcinoma (HCC) development; however, its post-translational modifications and regulatory mechanisms in HCC remain largely unexplored. Here, the expression levels of PGRN, OGT, and O-GlcNAcylation were found to be elevated in both HCC samples and cell lines. LC-MS/MS analysis and immunoprecipitation revealed that PGRN underwent O-linked N-acetylglucosamine (O-GlcNAc) modification at threonine 272 (Thr272). Co-immunoprecipitation and confocal microscopy confirmed the interaction and colocalization of O-GlcNAc transferase (OGT) with PGRN. Reducing O-GlcNAcylation increased the ubiquitination of PGRN, while increasing O-GlcNAcylation inhibited ubiquitination and elevated PGRN stability, as measured by cycloheximide (CHX) chase experiments. This regulation of PGRN stability was directly linked to its expression levels. Moreover, mutation at the primary O-GlcNAc site Thr272 inhibited the activity of the PI3K/AKT/mTOR signaling pathway and suppressed HCC cell proliferation. Together, our findings indicate that O-GlcNAcylation at Thr272 is essential for PGRN-driven HCC cell proliferation.","PeriodicalId":8779,"journal":{"name":"Biochemical and biophysical research communications","volume":"742 ","pages":"151150"},"PeriodicalIF":2.5,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142805898","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

cIAP2 supports the cell growth-promoting activity of FMR1 in gastric cancer via CARD-RING domains.

IF 2.5 3区生物学

Biochemical and biophysical research communications Pub Date : 2025-01-01 Epub Date: 2024-12-14 DOI: 10.1016/j.bbrc.2024.151189

Yui Taek Lee, Ji Woo Kang, Jeong In Heo, Tae Woong Seo, Soon Ji Yoo

{"title":"cIAP2 supports the cell growth-promoting activity of FMR1 in gastric cancer via CARD-RING domains.","authors":"Yui Taek Lee, Ji Woo Kang, Jeong In Heo, Tae Woong Seo, Soon Ji Yoo","doi":"10.1016/j.bbrc.2024.151189","DOIUrl":"10.1016/j.bbrc.2024.151189","url":null,"abstract":"Fragile X Mental Retardation Protein 1 (FMR1) is a translational repressor crucial for regulating genes in the central nervous system. While a lack of FMR1 expression causes Fragile X Syndrome (FXS), its overexpression is implicated in various cancers, necessitating tight regulation of FMR1 protein levels for normal cell physiology. In this study, we report that FMR1 is upregulated in gastric cancer patients. Reducing FMR1 expression decreased cell growth in gastric cancer cell lines. The Smac Mimetic LCL161 reduced both FMR1 and cellular inhibitor of apoptosis protein 2 (cIAP2) levels. Suppressing cIAP2, but not cIAP1, led to decreased FMR1, while cIAP2 overexpression increased FMR1 in gastric cancer cells. We observed that cIAP2 is also upregulated in gastric cancer patients, with FMR1 and cIAP2 levels positively correlated in both gastric and colorectal cancers. Notably, cIAP2 binds FMR1 via its CARD domain, unlike most cIAP2 targets that bind the BIR domain. Furthermore, cIAP2 ubiquitinates FMR1 through its CARD-RING domains, stabilizing the protein without proteasomal degradation. FMR1, modulated by cIAP2, promotes gastric cancer cell growth. Collectively, our findings highlight FMR1's growth-promoting role in gastric cancer and reveal a novel function of cIAP2 in stabilizing FMR1 as an E3 ligase. These results suggest targeting cIAP2 could be an effective strategy for treating gastric cancer by downregulating both cIAP2 and FMR1.","PeriodicalId":8779,"journal":{"name":"Biochemical and biophysical research communications","volume":"743 ","pages":"151189"},"PeriodicalIF":2.5,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142852201","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