title: SIAH1-induced p34SEI-1 polyubiquitination/degradation mediates p53 preferential vitamin C cytotoxicity.
abstract: Vitamin C is considered as an important anticancer therapeutic agent although this view is debatable. In this study, we introduce a physiological mechanism demonstrating how vitamin C exerts anticancer activity that induces cell cycle arrest and apoptosis. Our previous and current data reveal that p53 tumor suppressor is the prerequisite factor for stronger anticancer effects of vitamin C. In addition, vitamin C-mediated cancer cell cytotoxicity appears to be achieved at least partly through the downregulation of the p34SEI-1 oncoprotein. Our previous study showed that p34SEI-1 increases the survival of various types of cancer cells by inhibiting their apoptosis. Present data suggest that vitamin C treatment decreases the p34SEI-1 expression at the protein level and therefore alleviates its anti-apoptotic activity. Of note, SIAH1, E3 ubiquitin ligase, appears to be responsible for the p34SEI-1 polyubiquitination and its subsequent degradation, which is dependent on p53. In summary, vitamin C increases cancer cell death by inducing SIAH1-mediated polyubiquitination/degradation of the p34SEI-1 oncoprotein in a p53-dependent manner.
authors.affiliation: Department of Life Systems, Sookmyung Women's University, Seoul 140-742, Republic of Korea.
authors.forename: Soonduck
authors.initials: S
authors.lastname: Lee
authors.affiliation: Department of Life Systems, Sookmyung Women's University, Seoul 140-742, Republic of Korea.
authors.forename: Jinsun
authors.initials: J
authors.lastname: Kim
authors.affiliation: Department of Life Systems, Sookmyung Women's University, Seoul 140-742, Republic of Korea.
authors.forename: Samil
authors.initials: S
authors.lastname: Jung
authors.affiliation: Department of Life Systems, Sookmyung Women's University, Seoul 140-742, Republic of Korea.
authors.forename: Chengping
authors.initials: C
authors.lastname: Li
authors.affiliation: Department of Life Systems, Sookmyung Women's University, Seoul 140-742, Republic of Korea.
authors.forename: Young
authors.initials: Y
authors.lastname: Yang
authors.affiliation: Department of Life Systems, Sookmyung Women's University, Seoul 140-742, Republic of Korea.
authors.forename: Keun Il
authors.initials: KI
authors.lastname: Kim
authors.affiliation: Department of Life Systems, Sookmyung Women's University, Seoul 140-742, Republic of Korea.
authors.forename: Jong-Seok
authors.initials: JS
authors.lastname: Lim
authors.affiliation: Department of Life Systems, Sookmyung Women's University, Seoul 140-742, Republic of Korea.
authors.forename: Yonghwan
authors.initials: Y
authors.lastname: Kim
authors.affiliation: Department of Life Systems, Sookmyung Women's University, Seoul 140-742, Republic of Korea.
authors.forename: Choong-Il
authors.initials: CI
authors.lastname: Cheon
authors.affiliation: Department of Life Systems, Sookmyung Women's University, Seoul 140-742, Republic of Korea.
authors.forename: Myeong-Sok
authors.initials: MS
authors.lastname: Lee
mesh_terms: D001205:Ascorbic Acid / Q000494:pharmacology*; D016923:Cell Death / Q000187:drug effects / Q000235:genetics; D003603:Cytotoxins / Q000494:pharmacology*; D045325:HCT116 Cells; D006801:Humans; D061986:MCF-7 Cells; D009369:Neoplasms / Q000378:metabolism / Q000473:pathology*; D009687:Nuclear Proteins / Q000378:metabolism* / Q000502:physiology*; D059748:Proteolysis / Q000187:drug effects; D015534:Trans-Activators / Q000378:metabolism*; D014157:Transcription Factors; D016159:Tumor Suppressor Protein p53 / Q000037:antagonists & inhibitors / Q000502:physiology*; D044767:Ubiquitin-Protein Ligases / Q000502:physiology*; D054875:Ubiquitination / Q000187:drug effects / Q000235:genetics; D000098563:Seven in Absentia Proteins
chemical_list: D003603:Cytotoxins; D009687:Nuclear Proteins; C402464:SERTAD1 protein, human; D015534:Trans-Activators; D014157:Transcription Factors; D016159:Tumor Suppressor Protein p53; D044767:Ubiquitin-Protein Ligases; D000098563:Seven in Absentia Proteins; D001205:Ascorbic Acid