Neddylation pathway regulates T-cell function by targeting an adaptor protein Shc and a protein kinase Erk signaling
文献类型：期刊论文
| 作者 | Jin, HS; Liao, LJ; Park, Y; Liu, YC |
| 刊名 | PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
 |
| 出版日期 | 2013 |
| 卷号 | 110期号:2页码:624-629 |
| 关键词 | allergy signal transduction posttranslational modification |
| 通讯作者 | Liu, YC (reprint author), La Jolla Inst Allergy & Immunol, Div Cell Biol, La Jolla, CA 92037 USA.,yuncail@liai.org |
| 英文摘要 | NEDD8 (neural precursor cell expressed, developmentally down-regulated 8) is a ubiquitin-like molecule whose action on modifying protein substrates is critical in various cellular functions but whose importance in the immune system is not well understood. Here we investigated the role of protein neddylation in regulating T-cell function using an in vivo knockdown technique. We found that reduced expression of Ubc12 in CD4(+) T cells led to impaired T-cell receptor/CD28-induced proliferation and cytokine production both in vitro and in vivo, accompanied by reduced Erk activation. These findings were recapitulated by treatment with MLN4924, an inhibitor of NEDD8-activating enzyme. Furthermore, Shc, an adaptor molecule between antigen receptors and the Ras/Erk pathway, was identified as a target for neddylation. Importantly, mice adoptively transferred with Ubc12 knockdown CD4(+) T cells showed markedly ameliorated allergic responses. This study thus identifies an important role for protein neddylation in T-cell function, which may serve as a therapeutic target for inflammatory diseases. |
| 学科主题 | Science & Technology - Other Topics |
| 类目[WOS] | Multidisciplinary Sciences |
| 关键词[WOS] | UBIQUITIN LIGASE ; ACTIVATION ; CONJUGATION ; CANCER ; SCF |
| 收录类别 | SCI |
| 语种 | 英语 |
| WOS记录号 | WOS:000313906600052 |
| 版本 | 出版稿 |
| 源URL | [http://202.127.25.143/handle/331003/348]  |
| 专题 | 上海生化细胞研究所_上海生科院生化细胞研究所 |
| 推荐引用方式 GB/T 7714 | Jin, HS,Liao, LJ,Park, Y,et al. Neddylation pathway regulates T-cell function by targeting an adaptor protein Shc and a protein kinase Erk signaling[J]. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA,2013,110(2):624-629. |
| APA | Jin, HS,Liao, LJ,Park, Y,&Liu, YC.(2013).Neddylation pathway regulates T-cell function by targeting an adaptor protein Shc and a protein kinase Erk signaling.PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA,110(2),624-629. |
| MLA | Jin, HS,et al."Neddylation pathway regulates T-cell function by targeting an adaptor protein Shc and a protein kinase Erk signaling".PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA 110.2(2013):624-629. |
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