JOURNAL OF CELL BIOLOGY
·
2023
·Vol. 222
·期 5
·e202201068
·
IF 7.8
Wang Xinyi,Jiang Xiao,Li Boran,Zheng Jiahua,Guo Jiansheng,Gao Lei,Du Mengjie,Weng Xialian,Li Lin,Chen She,Zhang Jingzi,Fang Lei,Liu Ting,Wang Liang,Liu Wei,Neculai Dante,Sun Qiming
Macroautophagy (autophagy) utilizes a serial of receptors to specifically recognize and degrade autophagy cargoes, including damaged organelles, to maintain cellular homeostasis. Upstream signals spatiotemporally regulate the biological functions of selective autophagy receptors through protein post-translational modifications (PTM) such as phosphorylation. However, it is unclear how acetylation directly controls autophagy receptors in selective autophagy. Here, we report that an ER-phagy receptor FAM134B is acetylated by CBP acetyltransferase, eliciting intense ER-phagy. Furthermore, FAM134B acetylation promoted CAMKII-mediated phosphorylation to sustain a mode of milder ER-phagy. Conversely, SIRT7 deacetylated FAM134B to temper its activities in ER-phagy to avoid excessive ER degradation. Together, this work provides further mechanistic insights into how ER-phagy receptor perceives environmental signals for fine-tuning of ER homeostasis and demonstrates how nucleus-derived factors are programmed to control ER stress by modulating ER-phagy.
研究领域:
细胞生物学
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分子生物学
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生物化学
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DOI
PubMed
高影响因子
ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS
·
2025
·
IF 3
Qun Gao,Qi Wang,Yanjiao Hu,Fangjie Xin,Jie Chen,Sha Yu,Xinli Chen,Qingqing Lv,Baoxia Cui,Jun Jiao,Xinlin Jiao
Purpose To investigate the impact of SIRT7 on the development of cervical cancer and its relationship with cuproptosis in cervical cancer. Method HeLa and SiHa cells were transfected with lentiviruses for SIRT7 overexpression and knockdown. The effects of SIRT7 on cervical cancer cell proliferation, apoptosis, invasion, and migration were analyzed using CCK8, plate cloning, flow cytometry, Transwell assays, and scratch assays. To verify the relationship between SIRT7 and cuproptosis, we utilized cuproptosis inhibitors and activators. Immunofluorescence, transmission electron microscope, flow cytometry, ELISA, and Western blot were used to analyze copper ion content, mitochondrial ultrastructure, cellular reactive oxygen species, mitochondrial membrane potential, pyruvate levels, cell viability and the cuproptosis-related proteins. Results SIRT7 enhanced the proliferation, migration, and invasion of HeLa and SiHa cells, inhibited apoptosis, and promoted cervical cancer growth. Knocking down SIRT7 caused cuproptosis of HeLa and SiHa cells, characterized by increased Cu 2+ content, disrupted mitochondrial structure, decreased membrane potential, elevated ROS production, and upregulation of cuproptosis-related proteins SLC31A1 and HSP70, and downregulation of FDX1, LIAS and DLAT. Low SIRT7 expression's effect on cuproptosis was reduced by TTM. SIRT7 overexpression inhibited cuproptosis, unlike SIRT7 knockdown. SIRT7 overexpression's inhibitory effect on cuproptosis is altered by rhSLC31A1. Conclusion SIRT7 was recognized as an oncogene in cervical cancer, which boosted cervical cancer cell proliferation and invasion, lowered intracellular copper levels, and prevented cuproptosis. SIRT7 downregulation triggered cuproptosis, inhibiting tumor cell growth.
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产品关联
DOI
PubMed
高影响因子
Animals
·
2026
·Vol. 16
·期 18
·2886
·
IF 3.2
Jun Li,Zhongying Li,Menghan Han,Mengfan Zhao,Zhuoying Li,Huibin Shi,Haoyuan Han,Kun Liu,Xing Liu,Kai Quan
Simple SummarySirt7, a member of the NAD+-dependent class III histone deacetylase family (Sirtuins), is involved in the regulation of multiple metabolic processes, including glucose homeostasis and energy balance, and plays a key regulatory role in lipid metabolism. The present study demonstrates that inhibition of Sirt7 increases the expression of SREBP1 and downstream lipogenic genes, thereby enhancing lipid droplet accumulation and triglyceride levels, while also improving the fatty acid profile. These findings help to elucidate the molecular mechanisms by which Sirt7 regulates lipid metabolism and provide a deeper understanding of the regulatory mechanisms underlying milk fat synthesis in mammary epithelial cells of dairy goats.Milk fat, a key nutritional component of milk, not only supplies energy and immune protection for offspring but also serves as a critical quality indicator for goat milk. Sirt7, one of the least studied members of the Sirtuins family, has been shown to play a regulatory role in lipid metabolism. This study investigated the regulatory role of Sirt7 in milk fat synthesis and fatty acid composition in dairy goat mammary epithelial cells (GMECs) using a Sirt7 inhibitor (ID: 97491). GMECs were treated with a Sirt7 inhibitor (ID: 97491), and cell viability was assessed via the CCK-8 assay, which confirmed that 15 μmol/L inhibitor had no cytotoxic effects. Functional analyses using RT-qPCR, Western blot, and GC-MS revealed that Sirt7 inhibition upregulated the expression ofSREBP1,CD36,ACC,SCD1, andELOVL6while downregulatingFOXO1andFABP1. At the protein level, the inhibitor reduced Sirt7, FOXO1. Additionally, Sirt7 inhibition increased intracellular lipid droplet and triglyceride content. GC-MS analysis showed that Sirt7 inhibition decreased C11:0; increased C16:0, C15:0, C20:0, C24:0, C16:1, and C18:1n9c; and decreased C20:5n3 (EPA). Collectively, these findings suggest that pharmacological inhibition of Sirt7 is associated with upregulation of SREBP1, disruption of lipid homeostasis, triglyceride accumulation, and altered fatty acid composition in GMECs. These results provide preliminary evidence for a potential regulatory role of Sirt7 in milk fat synthesis and lay a foundation for future mechanistic studies.
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DOI
高影响因子
Pharmaceuticals
·
2023
·Vol. 16
·期 1
·119
·
IF 4.6
Chen Zhang,Wu Zhong,Ying Cao,Bohao Liu,Xiaojun Tao,Zhuan Li
The treatment of liver cancer remains challenging due to the low responsiveness of advanced cancer to therapeutic options. Sorafenib is the first line chemotherapeutic drug for advanced liver cancer but is frequently associated with severe side effects lead to discontinuation of chemotherapy. We previously developed a specific SIRT7 inhibitor 2800Z, which suppressed tumor growth and enhanced the chemosensitivity of sorafenib. In this study, we constructed polylysine polymer nanoparticles modified with cholesterol and GSH-sensitive PEG (mPssPC) to load sorafenib (SOR) and the SIRT7 inhibitor 2800Z to form dual-loaded NPs ([email protected]) to reduce the toxicity and increase efficacy of sorafenib in liver cancer. The average size of[email protected]NPs was approximately 370 nm and the zeta potential was approximately 50–53 mV. We found that the release of the drugs exhibited pH sensitivity and was significantly accelerated in an acid release medium simulating the tumor environment. In addition,[email protected]NPs inhibited the proliferation and induced apoptosis of liver cancer cells in vitro. An in vivo study further revealed that[email protected]showed high specificity to the liver cancer but low affinity and toxicity to the main organs including the heart, kidneys, lungs, and liver. Our data thus further approved the combination of a SIRT7 inhibitor and sorafenib for the treatment of liver cancer and provided new drug delivery system for targeted therapy.Keywords:polylysine;sorafenib;SIRT7 inhibitor;GSH-sensitive PEG;tumor microenvironment;targeted therapy
研究领域:
药理学
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纳米技术
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肿瘤学
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药物递送系统
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产品关联
DOI
PubMed
高影响因子
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