HECT ubiquitin ligase Smurf1 targets the tumor suppressor ING2 for ubiquitination and degradation

Nie, Jing; Liu, Lin; Wu, Min; Xing, Guichun; He, Shan; Yin, Yuxin; Tian, Chunyan; He, Fuchu; Zhang, Lingqiang

doi:10.1016/j.febslet.2010.05.033

« Previous Next »FEBS Letters
Volume 584, Issue 14 , Pages 3005-3012, 16 July 2010

HECT ubiquitin ligase Smurf1 targets the tumor suppressor ING2 for ubiquitination and degradation

Edited by Noboru Mizushima

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
Lin Liu
- Department of General Surgery, General Hospital of Chinese PLA, 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
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
Shan He
- College of Life Science and Bio-Engineering, Beijing University of Technology, Beijing, China
Yuxin Yin
- Department of Pathology, School of Basic Medical Sciences, Peking University, Beijing, China
Chunyan Tian
- 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. Address: Department of Genomics and Proteomics, Beijing Institute of Radiation Medicine, Beijing, China. Fax: +86 10 68177417.
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. Address: 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. Address: Department of Genomics and Proteomics, Beijing Institute of Radiation Medicine, Beijing, China. Fax: +86 10 68177417.

Received 27 March 2010; received in revised form 12 May 2010; accepted 14 May 2010. published online 28 May 2010.

Abstract

Inhibitor of growth 2 (ING2) gene encodes a candidate tumor suppressor and is frequently reduced in many tumors. However, the mechanisms underlying the regulation of ING2, in particular its protein stability, are still unclear. Here we show that the homologous to E6AP carboxyl terminus (HECT)-type ubiquitin ligase Smad ubiquitination regulatory factor 1 (Smurf1) interacts with and targets ING2 for poly-ubiquitination and proteasomal degradation. Intriguingly, the ING2 binding domain in Smurf1 was mapped to the catalytic HECT domain. Furthermore, the C-terminal PHD domain of ING2 was required for Smurf1-mediated degradation. This study provided the first evidence that the stability of ING2 could be regulated by ubiquitin-mediated degradation.

Structured summary

MINT-7894271: ING2 (uniprotkb:Q9H160) binds (MI:0407) to Smurf1 (uniprotkb:Q9HCE7) by pull-down (MI:0096)

MINT-7894319, MINT-7894339: ING2 (uniprotkb:Q9H160) physically interacts (MI:0915) with Smurf1 (uniprotkb:Q9HCE7) by anti tag co-immunoprecipitation (MI:0007)

MINT-7894301: Smurf1 (uniprotkb:Q9HCE7) physically interacts (MI:0915) with ING2 (uniprotkb:Q9H160) by anti bait co-immunoprecipitation (MI:0006)

MINT-7894358: ING1b (uniprotkb:Q9UK53-2) physically interacts (MI:0915) with Smurf1 (uniprotkb:Q9HCE7) by anti tag co-immunoprecipitation (MI:0007)

MINT-7894249: ING2 (uniprotkb:Q9H160) physically interacts (MI:0915) with ubiquitin (uniprotkb:P62988) by anti tag co-immunoprecipitation (MI:0007)

Abbreviations: E3, ubiquitin-protein ligase, HECT, homologous to E6AP carboxyl terminus, ING2, inhibitor of growth 2, Nedd4, neural precursor cells-expressed developmentally-downregulated gene 4, NLS, nuclear localization sequences, PHD, plant homeodomain, PtdInsPs, phosphoinositides, Smurf1, Smad ubiquitination regulatory factor 1

Keywords: Inhibitor of growth 2, Tumor suppressor, Smad ubiquitination regulatory factor 1, Ubiquitination, Protein degradation

To access this article, please choose from the options below

PII: S0014-5793(10)00426-6

doi:10.1016/j.febslet.2010.05.033

Refers to corrigendum:

Corrigendum to “HECT ubiquitin ligase Smurf1 targets the tumor suppressor ING2 for ubiquitination and degradation” [FEBS Lett. 584 (2010) 3005–3012] , 09 December 2010
Jing Nie, Lin Liu, Min Wu, Guichun Xing, Shan He, Yuxin Yin, Chunyan Tian, Fuchu He, Lingqiang Zhang
FEBS Letters 3 January 2011 (Vol. 585, Issue 1, Page 266)
- Full Text
- PDF (167 KB)