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.
authors.affiliation: National Institute of Cancer Research, National Health Research Institutes, Zhunan, Miaoli Country, Taiwan.
authors.forename: Yi-Wen
authors.initials: YW
authors.lastname: Chang
authors.affiliation: Graduate Institute of Clinical Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan. Division of General Surgery, Department of Surgery, Shuang Ho Hospital, Taipei Medical University, New Taipei City, Taiwan.
authors.forename: Hsin-An
authors.initials: HA
authors.lastname: Chen
authors.affiliation: National Institute of Cancer Research, National Health Research Institutes, Zhunan, Miaoli Country, Taiwan. Graduate Program of Biotechnology in Medicine College of Life Science, National Tsing Hua University, Hsinchu, Taiwan.
authors.forename: Chi-Feng
authors.initials: CF
authors.lastname: Tseng
authors.affiliation: National Institute of Cancer Research, National Health Research Institutes, Zhunan, Miaoli Country, Taiwan.
authors.forename: Chih-Chen
authors.initials: CC
authors.lastname: Hong
authors.affiliation: National Institute of Cancer Research, National Health Research Institutes, Zhunan, Miaoli Country, Taiwan. Graduate Program of Biotechnology in Medicine College of Life Science, National Tsing Hua University, Hsinchu, Taiwan.
authors.forename: Jui-Ti
authors.initials: JT
authors.lastname: Ma
authors.affiliation: Graduate Institute of Cancer Biology, China Medical University, Taichung, Taiwan. Center for Molecular Medicine, China Medical University Hospital, Taichung, Taiwan. Department of Biotechnology, Asia University, Taichung, Taiwan. Department of Molecular and Cellular Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
authors.forename: Mien-Chie
authors.initials: MC
authors.lastname: Hung
authors.affiliation: Graduate Institute of Clinical Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan. Division of General Surgery, Department of Surgery, Shuang Ho Hospital, Taipei Medical University, New Taipei City, Taiwan.
authors.forename: Chih-Hsiung
authors.initials: CH
authors.lastname: Wu
authors.affiliation: Graduate Institute of Clinical Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan. Division of General Surgery, Department of Surgery, Shuang Ho Hospital, Taipei Medical University, New Taipei City, Taiwan.
authors.forename: Ming-Te
authors.initials: MT
authors.lastname: Huang
authors.affiliation: National Institute of Cancer Research, National Health Research Institutes, Zhunan, Miaoli Country, Taiwan. Graduate Institute of Cancer Biology, China Medical University, Taichung, Taiwan. Center for Molecular Medicine, China Medical University Hospital, Taichung, Taiwan. Department of Biotechnology, Asia University, Taichung, Taiwan.
authors.forename: Jen-Liang
authors.initials: JL
authors.lastname: Su
mesh_terms: D000107:Acetylation; D017500:Adenovirus E1A Proteins / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D017209:Apoptosis; D015153:Blotting, Western; D001943:Breast Neoplasms / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D002465:Cell Movement; D049109:Cell Proliferation; D050881:E1A-Associated p300 Protein / Q000235:genetics / Q000378:metabolism*; D000091342:Endoplasmic Reticulum Chaperone BiP; D005260:Female; D006360:Heat-Shock Proteins / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D007124:Immunoenzyme Techniques; D047468:Immunoprecipitation; D008175:Lung Neoplasms / Q000378:metabolism / Q000517:prevention & control* / Q000556:secondary; D051379:Mice; D016513:Mice, SCID; D011485:Protein Binding; D011499:Protein Processing, Post-Translational; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014407:Tumor Cells, Cultured; D054875:Ubiquitination; D023041:Xenograft Model Antitumor Assays
chemical_list: D017500:Adenovirus E1A Proteins; D000091342:Endoplasmic Reticulum Chaperone BiP; C000717247:HSPA5 protein, human; D006360:Heat-Shock Proteins; C000717248:Hspa5 protein, mouse; D012333:RNA, Messenger; D050881:E1A-Associated p300 Protein; C494360:EP300 protein, human