RNF125 is a Ubiquitin-Protein Ligase that Promotes p53 Degradation
Background/Aims: Although early studies show that Mdm2 is the primary E3 ubiquitin ligase for the p53 tumor suppressor, an increasing amount of data suggests that p53 ubiquitination and degradation are more complex than once thought. Here, we investigated the role of RNF125, a non-Mdm2 ubiquitin-pro...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
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Cell Physiol Biochem Press GmbH & Co KG
2015-01-01
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| Series: | Cellular Physiology and Biochemistry |
| Subjects: | |
| Online Access: | http://www.karger.com/Article/FullText/369691 |
| _version_ | 1818321706501013504 |
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| author | Liuzhong Yang Bing Zhou Xiaorui Li Zhihong Lu Weiwei Li Xiaoqing Huo Zhanhui Miao |
| author_facet | Liuzhong Yang Bing Zhou Xiaorui Li Zhihong Lu Weiwei Li Xiaoqing Huo Zhanhui Miao |
| author_sort | Liuzhong Yang |
| collection | DOAJ |
| description | Background/Aims: Although early studies show that Mdm2 is the primary E3 ubiquitin ligase for the p53 tumor suppressor, an increasing amount of data suggests that p53 ubiquitination and degradation are more complex than once thought. Here, we investigated the role of RNF125, a non-Mdm2 ubiquitin-protein ligase, in the regulation of p53. Methods and Results: RNF125 physically interacted with p53 in exogenous/endogenous co-immunoprecipitation (IP) and GST-pull down assay, and a C72/75A mutation of RNF125 did not interfere with this interaction. Expression of RNF125 decreased the level of p53 in a dose-dependent manner, whereas knockdown of RNF125 by RNA interference increased the level of p53. As shown by Western blotting and ubiquitin assay, RNF125 ubiquitinated p53 and targeted it for proteasome degradation. Furthermore, RNF125 repressed p53 functions including p53-dependent transactivation and growth inhibition. Conclusion: Our data suggest that RNF125 negatively regulates p53 function through physical interaction and ubiquitin-mediated proteasome degradation. |
| first_indexed | 2024-12-13T10:45:10Z |
| format | Article |
| id | doaj.art-73ee84b3daf649c5ba5f11abda59b890 |
| institution | Directory Open Access Journal |
| issn | 1015-8987 1421-9778 |
| language | English |
| last_indexed | 2024-12-13T10:45:10Z |
| publishDate | 2015-01-01 |
| publisher | Cell Physiol Biochem Press GmbH & Co KG |
| record_format | Article |
| series | Cellular Physiology and Biochemistry |
| spelling | doaj.art-73ee84b3daf649c5ba5f11abda59b8902022-12-21T23:50:16ZengCell Physiol Biochem Press GmbH & Co KGCellular Physiology and Biochemistry1015-89871421-97782015-01-0135123724510.1159/000369691369691RNF125 is a Ubiquitin-Protein Ligase that Promotes p53 DegradationLiuzhong YangBing ZhouXiaorui LiZhihong LuWeiwei LiXiaoqing HuoZhanhui MiaoBackground/Aims: Although early studies show that Mdm2 is the primary E3 ubiquitin ligase for the p53 tumor suppressor, an increasing amount of data suggests that p53 ubiquitination and degradation are more complex than once thought. Here, we investigated the role of RNF125, a non-Mdm2 ubiquitin-protein ligase, in the regulation of p53. Methods and Results: RNF125 physically interacted with p53 in exogenous/endogenous co-immunoprecipitation (IP) and GST-pull down assay, and a C72/75A mutation of RNF125 did not interfere with this interaction. Expression of RNF125 decreased the level of p53 in a dose-dependent manner, whereas knockdown of RNF125 by RNA interference increased the level of p53. As shown by Western blotting and ubiquitin assay, RNF125 ubiquitinated p53 and targeted it for proteasome degradation. Furthermore, RNF125 repressed p53 functions including p53-dependent transactivation and growth inhibition. Conclusion: Our data suggest that RNF125 negatively regulates p53 function through physical interaction and ubiquitin-mediated proteasome degradation.http://www.karger.com/Article/FullText/369691RNF125p53E3 ubiquitin ligaseProteasome degradation |
| spellingShingle | Liuzhong Yang Bing Zhou Xiaorui Li Zhihong Lu Weiwei Li Xiaoqing Huo Zhanhui Miao RNF125 is a Ubiquitin-Protein Ligase that Promotes p53 Degradation Cellular Physiology and Biochemistry RNF125 p53 E3 ubiquitin ligase Proteasome degradation |
| title | RNF125 is a Ubiquitin-Protein Ligase that Promotes p53 Degradation |
| title_full | RNF125 is a Ubiquitin-Protein Ligase that Promotes p53 Degradation |
| title_fullStr | RNF125 is a Ubiquitin-Protein Ligase that Promotes p53 Degradation |
| title_full_unstemmed | RNF125 is a Ubiquitin-Protein Ligase that Promotes p53 Degradation |
| title_short | RNF125 is a Ubiquitin-Protein Ligase that Promotes p53 Degradation |
| title_sort | rnf125 is a ubiquitin protein ligase that promotes p53 degradation |
| topic | RNF125 p53 E3 ubiquitin ligase Proteasome degradation |
| url | http://www.karger.com/Article/FullText/369691 |
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