Stk40 deletion elevates c-JUN protein level and impairs mesoderm differentiation
文献类型：期刊论文
| 作者 | Hu, Jing3,4; Li, Shuang3,4; Sun, Xiaozhi3,4; Wang, Lina3,4; Ge, Laixiang3,4; Tang, Fan3,4; Gu, Junjie3,4; Yu, Hongyao3,4; Liao, Bing3,4; Jin, Ying3,4,5 |
| 刊名 | JOURNAL OF BIOLOGICAL CHEMISTRY
 |
| 出版日期 | 2019 |
| 卷号 | 294期号:25页码:9959-9972 |
| 关键词 | cell differentiation protein degradation development protein complex Wnt pathway c-JUN COP1 mesoderm differentiation protein stability STK40 |
| ISSN号 | 1554-8627 |
| DOI | 10.1074/jbc.RA119.007840 |
| 文献子类 | Article |
| 英文摘要 | Mesoderm development is a finely tuned process initiated by the differentiation of pluripotent epiblast cells. Serine/threonine kinase 40 (STK40) controls the development of several mesoderm-derived cell types, its overexpression induces differentiation of mouse embryonic stem cells (mESCs) toward the extraembryonic endoderm, and Stk40 knockout (KO) results in multiple organ failure and is lethal at the perinatal stage in mice. However, molecular mechanisms underlying the physiological functions of STK40 in mesoderm differentiation remain elusive. Here, we report that Stk40 ablation impairs mesoderm differentiation both in vitro and in vivo. Mechanistically, STK40 interacts with both the E3 ubiquitin ligase mammalian constitutive photomorphogenesis protein 1 (COP1) and the transcriptional regulator proto-oncogene c-Jun (c-JUN), promoting c-JUN protein degradation. Consequently, Stk40 knockout leads to c-JUN protein accumulation, which, in turn, apparently suppresses WNT signaling activity and impairs the mesoderm differentiation process. Overall, this study reveals that STK40, together with COP1, represents a previously unknown regulatory axis that modulates the c-JUN protein level within an appropriate range during mesoderm differentiation from mESCs. Our findings provide critical insights into the molecular mechanisms regulating the c-JUN protein level and may have potential implications for managing cellular disorders arising from c-JUN dysfunction. |
| 学科主题 | Biochemistry & Molecular Biology |
| WOS关键词 | EMBRYONIC STEM-CELLS ; UBIQUITIN LIGASE ; TUMOR-SUPPRESSOR ; BETA-CATENIN ; AP-1 ; INDUCTION ; COMPLEX ; COP1 ; WNT ; SPECIFICATION |
| 语种 | 英语 |
| WOS记录号 | WOS:000473277900026 |
| 出版者 | AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC |
| 版本 | 出版稿 |
| 源URL | [http://202.127.25.144/handle/331004/559]  |
| 专题 | 中国科学院上海生命科学研究院营养科学研究所 |
| 作者单位 | 1.Nanjing Med Univ, Dept Histol & Embryol, State Key Lab Reprod Med, Nanjing 211166, Jiangsu, Peoples R China, 2.ShanghaiTech Univ, Sch Life Sci & Technol, 100 Haike Rd, Shanghai 201210, Peoples R China; 3.Shanghai Jiao Tong Univ, Sch Med, Basic Clin Res Ctr, Renji Hosp, 227 South Chongqing Rd, Shanghai 200025, Peoples R China; 4.Shanghai Jiao Tong Univ, Sch Med, Shanghai Key Lab Reprod Med, Dept Histoembryol Genet & Dev Biol, 227 South Chongqing Rd, Shanghai 200025, Peoples R China; 5.Univ Chinese Acad Sci, CAS Key Lab Tissue Microenvironm & Tumor, CAS Ctr Excellence Mol Cell Sci,Chinese Acad Sci, Shanghai Inst Nutr & Hlth,Shanghai Inst Biol Sci, 320 Yueyang Rd, Shanghai 200032, Peoples R China; |
| 推荐引用方式 GB/T 7714 | Hu, Jing,Li, Shuang,Sun, Xiaozhi,et al. Stk40 deletion elevates c-JUN protein level and impairs mesoderm differentiation[J]. JOURNAL OF BIOLOGICAL CHEMISTRY,2019,294(25):9959-9972. |
| APA | Hu, Jing.,Li, Shuang.,Sun, Xiaozhi.,Wang, Lina.,Ge, Laixiang.,...&,.(2019).Stk40 deletion elevates c-JUN protein level and impairs mesoderm differentiation.JOURNAL OF BIOLOGICAL CHEMISTRY,294(25),9959-9972. |
| MLA | Hu, Jing,et al."Stk40 deletion elevates c-JUN protein level and impairs mesoderm differentiation".JOURNAL OF BIOLOGICAL CHEMISTRY 294.25(2019):9959-9972. |
入库方式： OAI收割
来源：上海营养与健康研究所
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