Wwp2 mediates oct4 ubiquitination and its own auto-ubiquitination in a dosage-dependent manner
文献类型：期刊论文
| 作者 | Liao, Bing1,2,3; Jin, Ying1,2,4 |
| 刊名 | Cell research
 |
| 出版日期 | 2010-03-01 |
| 卷号 | 20期号:3页码:332-344 |
| 关键词 | Degradation Embryonal carcinoma cells Oct4 Auto-ubiquitination Ubiquitin chain linkage Wwp2 |
| ISSN号 | 1001-0602 |
| DOI | 10.1038/cr.2009.136 |
| 通讯作者 | Jin, ying(yjin@sibs.ac.cn) |
| 英文摘要 | Transcription factor oct4 plays critical roles in maintaining pluripotency and controlling lineage commitment of embryonic stem cells (escs). our previous study indicates that wwp2, a mouse hect-type e3 ubiquitin ligase, ubiquitinates oct4 and promotes its degradation in a heterologous system. however, roles of wwp2 in regulating endogenous oct4 protein levels as well as molecular characteristics of the function of wwp2 have not been determined. here, we report that wwp2 plays an important role in oct4 ubiquitination and degradation during differentiation of embryonal carcinoma cells (eccs), although it does not appear to affect oct4 protein levels in the undifferentiated eccs and escs. importantly, inhibition of wwp2 expression by specific rna interference elevates the oct4 protein level, leading to attenuation in retinoid acid-induced activation of differentiation-related marker genes. mechanistically, wwp2 catalyzes oct4 poly-ubiquitination via the lysine 63 linkage in a dosage-dependent manner. interestingly, wwp2 also regulates its own ligase activity in a similar manner. moreover, auto-ubiquitination of wwp2 occurs through an intra-molecular mechanism. taken together, these results demonstrate a crucial role of wwp2 in controlling endogenous oct4 protein levels during differentiation processes of eccs and suggest an interesting dosage-dependent mechanism for regulating the catalytic activity of the e3 ubiquitin ligase, wwp2. |
| WOS关键词 | TRANSCRIPTION FACTOR OCT-4 ; EMBRYONIC STEM-CELLS ; E3 LIGASE ITCH ; PROTEIN LIGASE ; POLYUBIQUITIN CHAINS ; POU DOMAIN ; C2 DOMAIN ; DIFFERENTIATION ; DEGRADATION ; ACTIVATION |
| WOS研究方向 | Cell Biology |
| WOS类目 | Cell Biology |
| 语种 | 英语 |
| WOS记录号 | WOS:000275816300009 |
| 出版者 | INST BIOCHEMISTRY & CELL BIOLOGY |
| URI标识 | http://www.irgrid.ac.cn/handle/1471x/2410289 |
| 专题 | 中国科学院大学 |
| 通讯作者 | Jin, Ying |
| 作者单位 | 1.Shanghai Jiao Tong Univ, Chinese Acad Sci, Shanghai Inst Biol Sci, Inst Hlth Sci,Key Lab Stem Cell Biol,Sch Med, Shanghai 200025, Peoples R China 2.Shanghai Jiao Tong Univ, Sch Med, Shanghai Stem Cell Inst, Shanghai 200025, Peoples R China 3.Chinese Acad Sci, Grad Sch, Beijing 100000, Peoples R China 4.Shanghai Jiao Tong Univ, Sch Med, Chinese Minist Educ, Key Lab Cell Differentiat & Apoptosis, Shanghai 200025, Peoples R China |
| 推荐引用方式 GB/T 7714 | Liao, Bing,Jin, Ying. Wwp2 mediates oct4 ubiquitination and its own auto-ubiquitination in a dosage-dependent manner[J]. Cell research,2010,20(3):332-344. |
| APA | Liao, Bing,&Jin, Ying.(2010).Wwp2 mediates oct4 ubiquitination and its own auto-ubiquitination in a dosage-dependent manner.Cell research,20(3),332-344. |
| MLA | Liao, Bing,et al."Wwp2 mediates oct4 ubiquitination and its own auto-ubiquitination in a dosage-dependent manner".Cell research 20.3(2010):332-344. |
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来源：中国科学院大学
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