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; Jen Liang Su

doi:10.18632/oncotarget.2510

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, Jen Liang Su

Research output: Contribution to journal › Article › peer-review

28 Citations (Scopus)

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.

Original language	English
Pages (from-to)	10558-10570
Number of pages	13
Journal	Oncotarget
Volume	5
Issue number	21
DOIs	https://doi.org/10.18632/oncotarget.2510
Publication status	Published - 2014

Keywords

Acetylation
Adenovirus type 5 E1A
HSPA5/GRP78/Bip
Metastasis
Ubiquitination

ASJC Scopus subject areas

Oncology

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.18632/oncotarget.2510

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

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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author = "Chang, {Yi Wen} and Chen, {Hsin An} and Tseng, {Chi Feng} and Hong, {Chih Chen} and Ma, {Jui Ti} and Hung, {Mien Chie} and Wu, {Chih Hsiung} and Huang, {Ming Te} and Su, {Jen Liang}",

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T1 - De-acetylation and degradation of HSPA5 is critical for E1A metastasis suppression in breast cancer cells

AU - Chang, Yi Wen

AU - Chen, Hsin An

AU - Tseng, Chi Feng

AU - Hong, Chih Chen

AU - Ma, Jui Ti

AU - Hung, Mien Chie

AU - Wu, Chih Hsiung

AU - Huang, Ming Te

AU - Su, Jen Liang

PY - 2014

Y1 - 2014

N2 - 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.

AB - 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.

KW - Acetylation

KW - Adenovirus type 5 E1A

KW - HSPA5/GRP78/Bip

KW - Metastasis

KW - Ubiquitination

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

Abstract

Keywords

ASJC Scopus subject areas

UN SDGs

Access to Document

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