| Id |
Subject |
Object |
Predicate |
Lexical cue |
| T1 |
0-88 |
Sentence |
denotes |
Wwp2, an E3 ubiquitin ligase that targets transcription factor Oct-4 for ubiquitination. |
| T2 |
89-201 |
Sentence |
denotes |
The POU transcription factor Oct-4 is a master regulator affecting the fate of pluripotent embryonic stem cells. |
| T3 |
202-326 |
Sentence |
denotes |
However, the precise mechanisms by which the activation and expression of Oct-4 are regulated still remain to be elucidated. |
| T4 |
327-480 |
Sentence |
denotes |
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. |
| T5 |
481-588 |
Sentence |
denotes |
Remarkably, the expression of a catalytically inactive point mutant of Wwp2 abolishes Oct-4 ubiquitination. |
| T6 |
589-674 |
Sentence |
denotes |
Moreover, Wwp2 promotes Oct-4 degradation in the presence of overexpressed ubiquitin. |
| T7 |
675-741 |
Sentence |
denotes |
The degradation is blocked by treatment with proteasome inhibitor. |
| T8 |
742-868 |
Sentence |
denotes |
Fusion of a single ubiquitin to Oct-4 inactivates its transcriptional activity in a heterologous Oct-4-driven reporter system. |
| T9 |
869-988 |
Sentence |
denotes |
Furthermore, overexpression of Wwp2 in embryonic stem cells significantly reduces the Oct-4-transcriptional activities. |
| T10 |
989-1183 |
Sentence |
denotes |
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. |
| T11 |
1184-1420 |
Sentence |
denotes |
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. |
