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.
Authors	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
Journal	Oncotarget (Oncotarget) Vol. 5 Issue 21 Pg. 10558-70 (Nov 15 2014) ISSN: 1949-2553 [Electronic] United States
PMID	25301734 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References	Adenovirus E1A Proteins Endoplasmic Reticulum Chaperone BiP HSPA5 protein, human Heat-Shock Proteins Hspa5 protein, mouse RNA, Messenger E1A-Associated p300 Protein EP300 protein, human
Topics	Acetylation Adenovirus E1A Proteins (genetics, metabolism) Animals Apoptosis Blotting, Western Breast Neoplasms (metabolism, pathology, prevention & control) Cell Movement Cell Proliferation E1A-Associated p300 Protein (genetics, metabolism) Endoplasmic Reticulum Chaperone BiP Female Heat-Shock Proteins (genetics, metabolism) Humans Immunoenzyme Techniques Immunoprecipitation Lung Neoplasms (metabolism, prevention & control, secondary) Mice Mice, SCID Protein Binding Protein Processing, Post-Translational RNA, Messenger (genetics) Real-Time Polymerase Chain Reaction Reverse Transcriptase Polymerase Chain Reaction Tumor Cells, Cultured Ubiquitination Xenograft Model Antitumor Assays

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