title: A novel proapoptotic gene PANO encodes a post-translational modulator of the tumor suppressor p14ARF.
abstract: The protein p14ARF is a known tumor suppressor protein controlling cell proliferation and survival, which mainly localizes in nucleoli. However, the regulatory mechanisms that govern its activity or expression remain unclear. Here, we report that a novel proapoptotic nucleolar protein, PANO, modulates the expression and activity of p14ARF in HeLa cells. Overexpression of PANO enhances the stability of p14ARF protein by protecting it from degradation, resulting in an increase in p14ARF expression levels. Overexpression of PANO also induces apoptosis under low serum conditions. This effect is dependent on the nucleolar localization of PANO and inhibited by knocking-down p14ARF. Alternatively, PANO siRNA treated cells exhibit a reduction in p14ARF protein levels. In addition, ectopic expression of PANO suppresses the tumorigenicity of HeLa cells in nude mice. These results indicate that PANO is a new apoptosis-inducing gene by modulating the tumor suppressor protein, p14ARF, and may itself be a new candidate tumor suppressor gene.
authors.affiliation: Cancer Cell Research Group, Research Institute for Microbial Diseases, Osaka University, 3-1 Yamadaoka, Suita 565-0871, Japan.
authors.forename: Akihiro
authors.initials: A
authors.lastname: Watari
authors.forename: Yang
authors.initials: Y
authors.lastname: Li
authors.forename: Shinji
authors.initials: S
authors.lastname: Higashiyama
authors.forename: Masuo
authors.initials: M
authors.lastname: Yutsudo
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000235:genetics*; D051017:Apoptosis Regulatory Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000502:physiology*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D016147:Genes, Tumor Suppressor; D006367:HeLa Cells; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D011499:Protein Processing, Post-Translational / Q000235:genetics*; D034741:RNA, Small Interfering / Q000494:pharmacology; D014162:Transfection; D025803:Tumor Suppressor Protein p14ARF / Q000235:genetics / Q000378:metabolism*; D023041:Xenograft Model Antitumor Assays
chemical_list: D051017:Apoptosis Regulatory Proteins; C570477:PANO1 protein, human; D034741:RNA, Small Interfering; D025803:Tumor Suppressor Protein p14ARF