Abstract
The POU transcription factor Oct-4 is a master regulator affecting the fate of pluripotent embryonic stem cells. However, the precise mechanisms by which the activation and expression of Oct-4 are regulated still remain to be elucidated. We describe here a novel murine ubiquitin ligase, Wwp2, that specifically interacts with Oct-4 and promotes its ubiquitination both in vivo and in vitro. Remarkably, the expression of a catalytically inactive point mutant of Wwp2 abolishes Oct-4 ubiquitination. Moreover, Wwp2 promotes Oct-4 degradation in the presence of overexpressed ubiquitin. The degradation is blocked by treatment with proteasome inhibitor. Fusion of a single ubiquitin to Oct-4 inactivates its transcriptional activity in a heterologous Oct-4-driven reporter system. Furthermore, overexpression of Wwp2 in embryonic stem cells significantly reduces the Oct-4-transcriptional activities. Collectively, we demonstrate for the first time that Oct-4 can be post-translationally modified by ubiquitination and that this modification dramatically suppresses its transcriptional activity. These results reveal that the functional status of Oct-4, in addition to its expression level, dictates its transcriptional activity, and the results open up a new avenue to understand how Oct-4 defines the fate of embryonic stem cells.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 23495-23503 |
| Number of pages | 9 |
| Journal | Journal of Biological Chemistry |
| Volume | 279 |
| Issue number | 22 |
| DOIs | |
| State | Published - May 28 2004 |
| Externally published | Yes |
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ASJC Scopus subject areas
- Biochemistry
Cite this
Wwp2, An E3 ubiquitin ligase that targets transcription factor Oct-4 for ubiquitination. / Xu, Hui Ming; Liao, Bing; Zhang, Qian Jun; Wang, Bei Bei; Li, Hui; Zhong, Xiao Min; Sheng, Hui Zhen; Zhao, Yingxin; Zhao, Ying Ming; Jin, Ying.
In: Journal of Biological Chemistry, Vol. 279, No. 22, 28.05.2004, p. 23495-23503.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Wwp2, An E3 ubiquitin ligase that targets transcription factor Oct-4 for ubiquitination
AU - Xu, Hui Ming
AU - Liao, Bing
AU - Zhang, Qian Jun
AU - Wang, Bei Bei
AU - Li, Hui
AU - Zhong, Xiao Min
AU - Sheng, Hui Zhen
AU - Zhao, Yingxin
AU - Zhao, Ying Ming
AU - Jin, Ying
PY - 2004/5/28
Y1 - 2004/5/28
N2 - The POU transcription factor Oct-4 is a master regulator affecting the fate of pluripotent embryonic stem cells. However, the precise mechanisms by which the activation and expression of Oct-4 are regulated still remain to be elucidated. We describe here a novel murine ubiquitin ligase, Wwp2, that specifically interacts with Oct-4 and promotes its ubiquitination both in vivo and in vitro. Remarkably, the expression of a catalytically inactive point mutant of Wwp2 abolishes Oct-4 ubiquitination. Moreover, Wwp2 promotes Oct-4 degradation in the presence of overexpressed ubiquitin. The degradation is blocked by treatment with proteasome inhibitor. Fusion of a single ubiquitin to Oct-4 inactivates its transcriptional activity in a heterologous Oct-4-driven reporter system. Furthermore, overexpression of Wwp2 in embryonic stem cells significantly reduces the Oct-4-transcriptional activities. Collectively, we demonstrate for the first time that Oct-4 can be post-translationally modified by ubiquitination and that this modification dramatically suppresses its transcriptional activity. These results reveal that the functional status of Oct-4, in addition to its expression level, dictates its transcriptional activity, and the results open up a new avenue to understand how Oct-4 defines the fate of embryonic stem cells.
AB - The POU transcription factor Oct-4 is a master regulator affecting the fate of pluripotent embryonic stem cells. However, the precise mechanisms by which the activation and expression of Oct-4 are regulated still remain to be elucidated. We describe here a novel murine ubiquitin ligase, Wwp2, that specifically interacts with Oct-4 and promotes its ubiquitination both in vivo and in vitro. Remarkably, the expression of a catalytically inactive point mutant of Wwp2 abolishes Oct-4 ubiquitination. Moreover, Wwp2 promotes Oct-4 degradation in the presence of overexpressed ubiquitin. The degradation is blocked by treatment with proteasome inhibitor. Fusion of a single ubiquitin to Oct-4 inactivates its transcriptional activity in a heterologous Oct-4-driven reporter system. Furthermore, overexpression of Wwp2 in embryonic stem cells significantly reduces the Oct-4-transcriptional activities. Collectively, we demonstrate for the first time that Oct-4 can be post-translationally modified by ubiquitination and that this modification dramatically suppresses its transcriptional activity. These results reveal that the functional status of Oct-4, in addition to its expression level, dictates its transcriptional activity, and the results open up a new avenue to understand how Oct-4 defines the fate of embryonic stem cells.
UR - http://www.scopus.com/inward/record.url?scp=2542469858&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=2542469858&partnerID=8YFLogxK
U2 - 10.1074/jbc.M400516200
DO - 10.1074/jbc.M400516200
M3 - Article
C2 - 15047715
AN - SCOPUS:2542469858
VL - 279
SP - 23495
EP - 23503
JO - Journal of Biological Chemistry
JF - Journal of Biological Chemistry
SN - 0021-9258
IS - 22
ER -