Dynamic Methylation of Numb by Set8 Regulates Its Binding to p53 and Apoptosis
文献类型：期刊论文
| 作者 | Dhami, GK; Liu, HD; Galka, M; Voss, C; Wei, R; Muranko, K; Kaneko, T; Cregan, SP; Li, L; Li, SSC |
| 刊名 | MOLECULAR CELL
 |
| 出版日期 | 2013 |
| 卷号 | 50期号:4页码:565-576 |
| 通讯作者 | Li, SSC (reprint author), Univ Western Ontario, Schulich Sch Med & Dent, Dept Biochem, London, ON N6A 5C1, Canada.,sli@uwo.ca |
| 英文摘要 | Although Numb exhibits its tumor-suppressive function in breast cancer in part by binding to and stabilizing p53, it is unknown how the Numb-p53 interaction is regulated in cells. We found that Numb is methylated in its phosphotyrosine-binding (PTB) domain by the lysine methyltransferase Set8. Moreover, methylation uncouples Numb from p53, resulting in increased p53 ubiquitination and degradation. While Numb promotes apoptosis in a p53-dependent manner, the apoptotic function is abolished when Numb is methylated by Set8 or the Lys methylation sites in Numb are mutated. Conversely, the Numb-p53 interaction and Numb-mediated apoptosis are significantly enhanced by depletion of Set8 from cancer cells or by treating the cells with doxorubicin, a chemotherapeutic drug that causes a reduction in the mRNA and protein levels of Set8. Our work identifies the Set8-Numb-p53 signaling axis as an important regulatory pathway for apoptosis and suggests a therapeutic strategy by targeting Numb methylation. |
| 学科主题 | Biochemistry & Molecular Biology; Cell Biology |
| 类目[WOS] | Biochemistry & Molecular Biology ; Cell Biology |
| 关键词[WOS] | LYSINE METHYLATION ; HISTONE METHYLATION ; LUNG-CANCER ; DNA-DAMAGE ; CELL FATE ; PROTEINS ; PHOSPHORYLATION ; ACETYLATION ; PROTEOMICS |
| 收录类别 | SCI |
| 语种 | 英语 |
| WOS记录号 | WOS:000319893600011 |
| 版本 | 出版稿 |
| 源URL | [http://202.127.25.143/handle/331003/373]  |
| 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 | Dhami, GK,Liu, HD,Galka, M,et al. Dynamic Methylation of Numb by Set8 Regulates Its Binding to p53 and Apoptosis[J]. MOLECULAR CELL,2013,50(4):565-576. |
| APA | Dhami, GK.,Liu, HD.,Galka, M.,Voss, C.,Wei, R.,...&Li, SSC.(2013).Dynamic Methylation of Numb by Set8 Regulates Its Binding to p53 and Apoptosis.MOLECULAR CELL,50(4),565-576. |
| MLA | Dhami, GK,et al."Dynamic Methylation of Numb by Set8 Regulates Its Binding to p53 and Apoptosis".MOLECULAR CELL 50.4(2013):565-576. |
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