title: SS-A/Ro52 promotes apoptosis by regulating Bcl-2 production.
abstract: SS-A/Ro52 (Ro52), an autoantigen in systemic autoimmune diseases such as systemic lupus erythematosus and Sjögren's syndrome, has E3 ligase activity to ubiquitinate proteins that protect against viral infection. To investigate Ro52's role during stress, we transiently knocked it down in HeLa cells by siRo52 transfection. We found that Ro52(low) HeLa cells were significantly more resistant to apoptosis than wild-type HeLa cells when stimulated by H(2)O(2)- or diamide-induced oxidative stress, IFN-α, IFN-γ and anti-Fas antibody, etoposide, or γ-irradiation. Furthermore, Ro52-mediated apoptosis was not influenced by p53 protein level in HeLa cells. Depleting Ro52 in HeLa cells caused Bcl-2, but not other Bcl-2 family molecules, to be upregulated. Taken together, our data showed that Ro52 is a universal proapoptotic molecule, and that its proapoptotic effect does not depend on p53, but is exerted through negative regulation of the anti-apoptotic protein Bcl-2. These findings shed light on a new physiological role for Ro52 that is important to intracellular immunity.
authors.affiliation: Department of Clinical Pathology and Immunology, Kobe University Graduate School of Medicine, Kobe, Hyogo, Japan.
authors.forename: Siti Nur Aisyah
authors.initials: SN
authors.lastname: Jauharoh
authors.forename: Jun
authors.initials: J
authors.lastname: Saegusa
authors.forename: Takeshi
authors.initials: T
authors.lastname: Sugimoto
authors.forename: Bambang
authors.initials: B
authors.lastname: Ardianto
authors.forename: Shimpei
authors.initials: S
authors.lastname: Kasagi
authors.forename: Daisuke
authors.initials: D
authors.lastname: Sugiyama
authors.forename: Chiyo
authors.initials: C
authors.lastname: Kurimoto
authors.forename: Osamu
authors.initials: O
authors.lastname: Tokuno
authors.forename: Yuji
authors.initials: Y
authors.lastname: Nakamachi
authors.forename: Shunichi
authors.initials: S
authors.lastname: Kumagai
authors.forename: Seiji
authors.initials: S
authors.lastname: Kawano
mesh_terms: D021581:Active Transport, Cell Nucleus; D017209:Apoptosis / Q000235:genetics / Q000276:immunology*; D002467:Cell Nucleus / Q000201:enzymology; D003958:Diamide / Q000494:pharmacology; D055785:Gene Knockdown Techniques; D006367:HeLa Cells; D006801:Humans; D006861:Hydrogen Peroxide / Q000494:pharmacology; D016898:Interferon-alpha / Q000494:pharmacology; D007371:Interferon-gamma / Q000494:pharmacology; D018384:Oxidative Stress / Q000235:genetics / Q000276:immunology*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000096:biosynthesis*; D012261:Ribonucleoproteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D000099207:SS-A Antigen
chemical_list: D003958:Diamide; D006861:Hydrogen Peroxide; D016898:Interferon-alpha; D007371:Interferon-gamma; D019253:Proto-Oncogene Proteins c-bcl-2; D012261:Ribonucleoproteins; D000099207:SS-A Antigen