Parp1 poly(adp-ribosyl)ates sox2 to control sox2 protein levels and fgf4 expression during embryonic stem cell differentiation
文献类型：期刊论文
| 作者 | Gao, Furong1,2,4; Kwon, Sung Won3; Zhao, Yingming3; Jin, Ying1,2 |
| 刊名 | Journal of biological chemistry
 |
| 出版日期 | 2009-08-14 |
| 卷号 | 284期号:33页码:22263-22273 |
| ISSN号 | 0021-9258 |
| DOI | 10.1074/jbc.m109.033118 |
| 通讯作者 | Jin, ying(yjin@sibs.ac.cn) |
| 英文摘要 | Transcription factors oct4 and sox2 are key players in maintaining the pluripotent state of embryonic stem cells (escs). small changes in their levels disrupt normal expression of their target genes. however, it remains elusive how protein levels of oct4 and sox2 and expression of their target genes are precisely controlled in escs. here we identify parp1, a dna-binding protein with an nad(+)-dependent enzymatic activity, as a cofactor of oct4 and sox2 to regulate expression of their target gene fgf4. we demonstrate for the first time that parp1 binds the fgf4 enhancer to positively regulate fgf4 expression. our data show that parp1 interacts with and poly(adp-ribosyl)ates sox2 directly, which may be a step required for dissociation and degradation of inhibitory sox2 proteins from the fgf4 enhancer. when parp1 activity is inhibited or absent, poly(adp-ribosyl)ation of sox2 decreases and association of sox2 with fgf4 enhancers increases, accompanied by an elevated level of sox2 proteins and reduced expression of fgf4. significantly, specific knockdown of sox2 expression by rna interference can considerably abrogate the inhibitory effect of the poly(adpribose) polymerase inhibitor on fgf4 expression. interestingly, parp1 deficiency does not affect undifferentiated escs but compromises cell survival and/or growth when escs are induced into differentiation. addition of fgf4 can partially rescue the phenotypes caused by parp1 deficiency during esc differentiation. taken together, this study uncovers new mechanisms through which sox2 protein levels and fgf4 expression are dynamically regulated during esc differentiation and adds a new member to the family of proteins regulating the properties of escs. |
| WOS关键词 | NF-KAPPA-B ; TRANSCRIPTION FACTOR OCT-4 ; NANOG GENE-EXPRESSION ; CARCINOMA-CELLS ; SELF-RENEWAL ; POSTTRANSLATIONAL MODIFICATION ; REGULATORY ELEMENT ; SYNERGISTIC ACTION ; MOUSE DEVELOPMENT ; ADP-RIBOSYLATION |
| WOS研究方向 | Biochemistry & Molecular Biology |
| WOS类目 | Biochemistry & Molecular Biology |
| 语种 | 英语 |
| WOS记录号 | WOS:000268783700050 |
| 出版者 | AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC |
| URI标识 | http://www.irgrid.ac.cn/handle/1471x/2404012 |
| 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, Sch Med,Inst Hlth Sci,Key Lab Stem Cell Biol, Shanghai 200025, Peoples R China 2.Shanghai Jiao Tong Univ, Sch Med, Shanghai Stem Cell Inst, Shanghai 200025, Peoples R China 3.Univ Chicago, Ben May Dept Canc Res, Chicago, IL 60637 USA 4.Chinese Acad Sci, Grad Sch, Beijing 100000, Peoples R China |
| 推荐引用方式 GB/T 7714 | Gao, Furong,Kwon, Sung Won,Zhao, Yingming,et al. Parp1 poly(adp-ribosyl)ates sox2 to control sox2 protein levels and fgf4 expression during embryonic stem cell differentiation[J]. Journal of biological chemistry,2009,284(33):22263-22273. |
| APA | Gao, Furong,Kwon, Sung Won,Zhao, Yingming,&Jin, Ying.(2009).Parp1 poly(adp-ribosyl)ates sox2 to control sox2 protein levels and fgf4 expression during embryonic stem cell differentiation.Journal of biological chemistry,284(33),22263-22273. |
| MLA | Gao, Furong,et al."Parp1 poly(adp-ribosyl)ates sox2 to control sox2 protein levels and fgf4 expression during embryonic stem cell differentiation".Journal of biological chemistry 284.33(2009):22263-22273. |
入库方式： iSwitch采集
来源：中国科学院大学
浏览0
下载0
收藏0
其他版本
除非特别说明，本系统中所有内容都受版权保护，并保留所有权利。