REGγ proteasome mediates degradation of the ubiquitin ligase Smurf1

Nie, Jing; Wu, Min; Wang, Jian; Xing, Guichun; He, Fuchu; Zhang, Lingqiang

doi:10.1016/j.febslet.2010.05.034

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Volume 584, Issue 14 , Pages 3021-3027, 16 July 2010

REGγ proteasome mediates degradation of the ubiquitin ligase Smurf1

Edited by Zhijie Chang

Jing Nie
- Department of Biology Sciences and Biotechnology, Tsinghua University, Beijing, China
- State Key Laboratory of Proteomics, Beijing Proteome Research Center, Beijing Institute of Radiation Medicine, Beijing, China
Min Wu
- Laboratory of Molecular Biology and Department of Biochemistry, Key Laboratory of Gene Resource Utilization for Severe Disease, Anhui Medical University, Hefei, Anhui Province, China
Jian Wang
- Department of Biology Sciences and Biotechnology, Tsinghua University, Beijing, China
- State Key Laboratory of Proteomics, Beijing Proteome Research Center, Beijing Institute of Radiation Medicine, Beijing, China
Guichun Xing
- Department of Biology Sciences and Biotechnology, Tsinghua University, Beijing, China
- State Key Laboratory of Proteomics, Beijing Proteome Research Center, Beijing Institute of Radiation Medicine, Beijing, China
Fuchu He
- Department of Biology Sciences and Biotechnology, Tsinghua University, Beijing, China
- State Key Laboratory of Proteomics, Beijing Proteome Research Center, Beijing Institute of Radiation Medicine, Beijing, China
- Corresponding author at: Department of Genomics and Proteomics, Beijing Institute of Radiation Medicine, Beijing, China. Fax: +86 10 68177417.
Lingqiang Zhang
- Department of Biology Sciences and Biotechnology, Tsinghua University, Beijing, China
- State Key Laboratory of Proteomics, Beijing Proteome Research Center, Beijing Institute of Radiation Medicine, Beijing, China
- Laboratory of Molecular Biology and Department of Biochemistry, Key Laboratory of Gene Resource Utilization for Severe Disease, Anhui Medical University, Hefei, Anhui Province, China
- Corresponding author at: Department of Genomics and Proteomics, Beijing Institute of Radiation Medicine, Beijing, China. Fax: +86 10 68177417.

Received 27 April 2010; received in revised form 12 May 2010; accepted 14 May 2010. published online 24 May 2010.

Abstract

The ubiquitin ligase Smad ubiquitination regulatory factor 1 (Smurf1) targets many proteins including Smad1/5 for ubiquitin-dependent proteasomal degradation. However, how Smurf1 is degraded remains unclear. Here we show that REGγ, an activator for the 20S proteasome-mediated protein degradation, interacts with Smurf1 and mediates its degradation. We provide evidence that depletion of REGγ stabilizes Smurf1 whereas overexpression of REGγ promotes the degradation of Smurf1. Interestingly both Smurf2 and Smurf1 are destabilized by the REGγ proteasome while the other members of Neural precursor cell-expressed developmentally downregulated gene 4 family were not affected. More importantly, we found that the REGγ proteasome-mediated degradation of Smurf1 results in degradation of Smad5. These findings reveal that the REGγ-proteasome targets a ubiquitin ligase for protein degradation.

Structured summary

MINT-7894509: CKIP (uniprotkb:Q53GL0) binds (MI:0407) to Smurf1 (uniprotkb:Q9HCE7) by pull down (MI:0096)

MINT-7894494: REG gamma (uniprotkb:P61289) binds (MI:0407) to Smurf1 (uniprotkb:Q9HCE7) by pull down (MI:0096)

MINT-7894523, MINT-7894543, MINT-7894481: REG gamma (uniprotkb:P61289) physically interacts (MI:0915) with Smurf1 (uniprotkb:Q9HCE7) by anti tag coimmunoprecipitation (MI:0007)

MINT-7894558: Smurf1 (uniprotkb:Q9HCE7) physically interacts (MI:0915) with REG gamma (uniprotkb:P61289) by two hybrid (MI:0018)

Keywords: Proteasome, Protein degradation, REGγ, Smad ubiquitination regulatory factor 1, Ubiquitin

Abbreviations: E3, ubiquitin-protein ligase, HECT, homologous to E6AP C-terminus, Nedd4, neural precursor cells-expressed developmentally-downregulated gene 4, Smurf1, Smad ubiquitination regulatory factor 1