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 journalArticle

11 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 languageEnglish
Pages (from-to)10558-10570
Number of pages13
JournalOncotarget
Volume5
Issue number21
Publication statusPublished - 2014

Fingerprint

Acetylation
Ubiquitination
Breast Neoplasms
Neoplasm Metastasis
Histone Acetyltransferases
Ubiquitin-Protein Ligases
Proteasome Endopeptidase Complex
Post Translational Protein Processing
Drug Resistance
Adenoviridae
Genetic Therapy
Neoplasms

Keywords

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

ASJC Scopus subject areas

  • Oncology

Cite this

Chang, Y. W., Chen, H. A., Tseng, C. F., Hong, C. C., Ma, J. T., Hung, M. C., ... Su, J. L. (2014). De-acetylation and degradation of HSPA5 is critical for E1A metastasis suppression in breast cancer cells. Oncotarget, 5(21), 10558-10570.

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.

In: Oncotarget, Vol. 5, No. 21, 2014, p. 10558-10570.

Research output: Contribution to journalArticle

Chang, YW, Chen, HA, Tseng, CF, Hong, CC, Ma, JT, Hung, MC, Wu, CH, Huang, MT & Su, JL 2014, 'De-acetylation and degradation of HSPA5 is critical for E1A metastasis suppression in breast cancer cells', Oncotarget, vol. 5, no. 21, pp. 10558-10570.
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. In: Oncotarget. 2014 ; Vol. 5, No. 21. pp. 10558-10570.
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