Oncotarget

Research Papers:

De-acetylation and degradation of HSPA5 is critical for E1A metastasis suppression in breast cancer cells

Yi-Wen Chang, Hsin-An Chen, Chi-Feng Tseng, Chih-Chen Hong, Jui-Ti Ma, Mien-Chie Hung, Chih-Hsiung Wu, Ming-Te Huang and Jen-Liang Su _

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Oncotarget. 2014; 5:10558-10570. https://doi.org/10.18632/oncotarget.2510

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Abstract

Yi-Wen Chang1,*, Hsin-An Chen2,3,*, Chi-Feng Tseng1,4, Chih-Chen Hong1, Jui-Ti Ma1,4, Mien-Chie Hung5,6,7,8, Chih-Hsiung Wu2,3, Ming-Te Huang2,3 and Jen-Liang Su1,5,6,7

1 National Institute of Cancer Research, National Health Research Institutes, Zhunan, Miaoli Country, Taiwan

2 Graduate Institute of Clinical Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan

3 Division of General Surgery, Department of Surgery, Shuang Ho Hospital, Taipei Medical University, New Taipei City, Taiwan

4 Graduate Program of Biotechnology in Medicine College of Life Science, National Tsing Hua University, Hsinchu, Taiwan

5 Graduate Institute of Cancer Biology, China Medical University, Taichung, Taiwan

6 Center for Molecular Medicine, China Medical University Hospital, Taichung, Taiwan

7 Department of Biotechnology, Asia University, Taichung, Taiwan

8 Department of Molecular and Cellular Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA

* These authors contributed equally to this work

Correspondence:

Jen-Liang Su , email:

Keywords: acetylation, adenovirus type 5 E1A, HSPA5/GRP78/Bip, metastasis, ubiquitination

Received: July 02, 2014 Accepted: September 24, 2014 Published: September 25, 2014

Abstract

Elevated expression of heat shock protein 5 (HSPA5) promotes drug resistance and metastasis and is a marker of poor prognosis in breast cancer patients. Adenovirus type 5 E1A gene therapy has demonstrated antitumor efficacy but the mechanisms of metastasis-inhibition are unclear. Here, we report that E1A interacts with p300 histone acetyltransferase (HAT) and blocks p300-mediated HSPA5 acetylation at K353, which in turn promotes HSPA5 ubiquitination by GP78 (E3 ubiquitin ligase) and subsequent proteasome-mediated degradation. Our findings point out the Ying-Yang regulation of two different post-translational modifications (ubiquitination and acetylation) of HSPA5 in tumor metastasis.


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