Serum-and glucocorticoid-induced kinase 3 orchestrates glucocorticoid signaling to facilitate chromatin remodeling during murine adipogenesis
文献类型：期刊论文
| 作者 | Chen, Qilong2; Guo, Jialu2; Liu, Yuyi2; Du, Tai2; Liu, Jiapei3; Zhang, Yuyao4,5,6; Dai, Yuming2; Zhang, Mengdi2; Zhou, Ziqian2; Zhang, Qiyang2 |
| 刊名 | JOURNAL OF CLINICAL INVESTIGATION
 |
| 出版日期 | 2025-10-01 |
| 卷号 | 135期号:19页码:21 |
| ISSN号 | 0021-9738 |
| DOI | 10.1172/JCI186534 |
| 英文摘要 | Elevated glucocorticoid levels are common in conditions such as aging, chronic stress, Cushing syndrome, and glucocorticoid therapy. While glucocorticoids suppress inflammation through the glucocorticoid receptor (GR), they also cause metabolic side effects. Investigating alternative pathways beyond GR activation is crucial for reducing these side effects. Our phosphoproteomics analysis revealed that glucocorticoid exposure promotes phosphorylation at the RxxS motifs of multiple proteins in preadipocytes, including those mediated by serum-and glucocorticoid-induced kinase 3 (SGI(3). SGI(3 is a key mediator of glucocorticoid-induced adipogenesis, as shown by impaired adipogenesis after SGI(3 inhibition or genetic ablation. Sgk3-I(O mice were resistant to obesity induced by glucocorticoid or a high-fat diet, and proteolysis targeting chimeras (PROTAC) targeting SGI(3 reduced adipogenesis in both obese mice and in a thyroid eye disease cell line. Mechanistically, SGI(3 translocated to the nucleus upon glucocorticoid stimulation, interacted with and phosphorylated the BRG1 subunit of the BAF complex, and prevented BRG1 degradation, promoting chromatin remodeling necessary for adipogenesis. These findings highlight SGI(3 as a potential therapeutic target to mitigate metabolic side effects of elevated glucocorticoid levels. |
| WOS关键词 | ACTIVATION ; SGK3 ; PHOSPHORYLATION ; HUMANS |
| 资助项目 | Science and Technology Major Project[2024ZD0530100] ; Talent Plan of Shanghai Branch-Chinese Academy of Sciences[CASSHB-QNPD-2023-019] |
| WOS研究方向 | Research & Experimental Medicine |
| 语种 | 英语 |
| WOS记录号 | WOS:001616098100005 |
| 出版者 | AMER SOC CLINICAL INVESTIGATION INC |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/321983]  |
| 专题 | 国家级研究中心_原创新药研究全国重点实验室 |
| 通讯作者 | Zhang, Fang; Soukas, Alexander A.; Zhou, Ben |
| 作者单位 | 1.Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Immune Response & Immunotherapy, Shanghai, Peoples R China 2.Chinese Acad Sci, Univ Chinese Acad Sci, Shanghai Inst Nutr & Hlth, Shanghai 200031, Peoples R China 3.Shanghai Jiao Tong Univ, Shanghai Gen Hosp, Natl Clin Res Ctr Eye Dis, Sch Med,Dept Ophthal, Shanghai 200080, Peoples R China 4.Massachusetts Gen Hosp, Dept Med, Diabet Unit, Boston, MA 02114 USA 5.Massachusetts Gen Hosp, Ctr Genom Med, Boston, MA USA 6.Harvard Med Sch, Boston, MA USA |
| 推荐引用方式 GB/T 7714 | Chen, Qilong,Guo, Jialu,Liu, Yuyi,et al. Serum-and glucocorticoid-induced kinase 3 orchestrates glucocorticoid signaling to facilitate chromatin remodeling during murine adipogenesis[J]. JOURNAL OF CLINICAL INVESTIGATION,2025,135(19):21. |
| APA | Chen, Qilong.,Guo, Jialu.,Liu, Yuyi.,Du, Tai.,Liu, Jiapei.,...&Zhou, Ben.(2025).Serum-and glucocorticoid-induced kinase 3 orchestrates glucocorticoid signaling to facilitate chromatin remodeling during murine adipogenesis.JOURNAL OF CLINICAL INVESTIGATION,135(19),21. |
| MLA | Chen, Qilong,et al."Serum-and glucocorticoid-induced kinase 3 orchestrates glucocorticoid signaling to facilitate chromatin remodeling during murine adipogenesis".JOURNAL OF CLINICAL INVESTIGATION 135.19(2025):21. |
入库方式： OAI收割
来源：上海药物研究所
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