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

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 tha...

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Autores principales: Chang, Yi-Wen, Chen, Hsin-An, Tseng, Chi-Feng, Hong, Chih-Chen, Ma, Jui-Ti, Hung, Mien-Chie, Wu, Chih-Hsiung, Huang, Ming-Te, Su, Jen-Liang
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Impact Journals LLC 2014
Materias:
Research Paper
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4279393/
https://www.ncbi.nlm.nih.gov/pubmed/25301734
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author Chang, Yi-Wen
Chen, Hsin-An
Tseng, Chi-Feng
Hong, Chih-Chen
Ma, Jui-Ti
Hung, Mien-Chie
Wu, Chih-Hsiung
Huang, Ming-Te
Su, Jen-Liang
author_facet Chang, Yi-Wen
Chen, Hsin-An
Tseng, Chi-Feng
Hong, Chih-Chen
Ma, Jui-Ti
Hung, Mien-Chie
Wu, Chih-Hsiung
Huang, Ming-Te
Su, Jen-Liang
author_sort Chang, Yi-Wen
collection PubMed
description 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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spelling pubmed-42793932015-01-06 De-acetylation and degradation of HSPA5 is critical for E1A metastasis suppression in breast cancer cells Chang, Yi-Wen Chen, Hsin-An Tseng, Chi-Feng Hong, Chih-Chen Ma, Jui-Ti Hung, Mien-Chie Wu, Chih-Hsiung Huang, Ming-Te Su, Jen-Liang Oncotarget Research Paper 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. Impact Journals LLC 2014-09-25 /pmc/articles/PMC4279393/ /pubmed/25301734 Text en Copyright: © 2014 Chang et al. http://creativecommons.org/licenses/by/2.5/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Paper
Chang, Yi-Wen
Chen, Hsin-An
Tseng, Chi-Feng
Hong, Chih-Chen
Ma, Jui-Ti
Hung, Mien-Chie
Wu, Chih-Hsiung
Huang, Ming-Te
Su, Jen-Liang
De-acetylation and degradation of HSPA5 is critical for E1A metastasis suppression in breast cancer cells
title De-acetylation and degradation of HSPA5 is critical for E1A metastasis suppression in breast cancer cells
title_full De-acetylation and degradation of HSPA5 is critical for E1A metastasis suppression in breast cancer cells
title_fullStr De-acetylation and degradation of HSPA5 is critical for E1A metastasis suppression in breast cancer cells
title_full_unstemmed De-acetylation and degradation of HSPA5 is critical for E1A metastasis suppression in breast cancer cells
title_short De-acetylation and degradation of HSPA5 is critical for E1A metastasis suppression in breast cancer cells
title_sort de-acetylation and degradation of hspa5 is critical for e1a metastasis suppression in breast cancer cells
topic Research Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4279393/
https://www.ncbi.nlm.nih.gov/pubmed/25301734
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