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Journal of Experimental & Clinical Cancer Research
Published in: Journal of Experimental & Clinical Cancer Research 1/2018

Open Access 01-12-2018 | Research

SPOP promotes ATF2 ubiquitination and degradation to suppress prostate cancer progression

Authors: Jian Ma, Kun Chang, Jingtao Peng, Qing Shi, Hualei Gan, Kun Gao, Kai Feng, Fujiang Xu, Hailiang Zhang, Bo Dai, Yao Zhu, Guohai Shi, Yijun Shen, Yiping Zhu, Xiaojian Qin, Yao Li, Pingzhao Zhang, Dingwei Ye, Chenji Wang

Published in: Journal of Experimental & Clinical Cancer Research | Issue 1/2018

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Abstract

Background

Next-generation sequencing of the exome and genome of prostate cancers has identified numerous genetic alterations. SPOP (Speckle-type POZ Protein) is one of the most frequently mutated genes in primary prostate cancer, suggesting that SPOP may be a potential driver of prostate cancer. The aim of this work was to investigate how SPOP mutations contribute to prostate cancer development and progression.

Methods

To identify molecular mediators of the tumor suppressive function of SPOP, we performed a yeast two-hybrid screen in a HeLa cDNA library using the full-length SPOP as bait. Immunoprecipitation and Western Blotting were used to analyze the interaction between SPOP and ATF2. Cell migration and invasion were determined by Transwell assays. Immunohistochemistry were used to analyze protein levels in patients’ tumor samples.

Results

Here we identified ATF2 as a bona fide substrate of the SPOP-CUL3-RBX1 E3 ubiquitin ligase complex. SPOP recognizes multiple Ser/Thr (S/T)-rich degrons in ATF2 and triggers ATF2 degradation via the ubiquitin-proteasome pathway. Strikingly, prostate cancer-associated mutants of SPOP are defective in promoting ATF2 degradation in prostate cancer cells and contribute to facilitating prostate cancer cell proliferation, migration and invasion.

Conclusion

SPOP promotes ATF2 ubiquitination and degradation, and ATF2 is an important mediator of SPOP inactivation-induced cell proliferation, migration and invasion.
Appendix
Available only for authorised users
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Metadata
Title
SPOP promotes ATF2 ubiquitination and degradation to suppress prostate cancer progression
Authors
Jian Ma
Kun Chang
Jingtao Peng
Qing Shi
Hualei Gan
Kun Gao
Kai Feng
Fujiang Xu
Hailiang Zhang
Bo Dai
Yao Zhu
Guohai Shi
Yijun Shen
Yiping Zhu
Xiaojian Qin
Yao Li
Pingzhao Zhang
Dingwei Ye
Chenji Wang
Publication date
01-12-2018
Publisher
BioMed Central
Published in
Journal of Experimental & Clinical Cancer Research / Issue 1/2018
Electronic ISSN: 1756-9966
DOI
https://doi.org/10.1186/s13046-018-0809-0

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