The p53-inducible TSAP6 gene product regulates apoptosis and the cell cycle and interacts with Nix and the Myt1 kinase
| Autor: | Robert Amson, Véronique Bouvard, Marcel Tuynder, Stephanie Morchoisne, Christophe Cans, Aude Roborel de Climens, Sylvie Prieur, Vanessa Nancy-Portebois, Laurent Susini, Brent Passer, Nathalie Amzallag, Giusy Fiucci, Virginie Crible, Adam Telerman, Jean Dausset, Alexandra Lespagnol, Moshe Oren |
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| Přispěvatelé: | Immunité et cancer (U932), Université Paris Descartes - Paris 5 (UPD5)-Institut Curie [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Laboratoire de Biologie Moléculaire de la Cellule (LBMC), École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Organisation Reconstruction Travail - ORT (FRANCE), Centre internationale de recherche sur le cancer, CHU Pontchaillou [Rennes], Service de Recherche en Hémato-Immunologie (SRHI - UMR_E 05), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris Diderot - Paris 7 (UPD7), Department of Molecular Cell Biology [Rehovot], Weizmann Institute of Science [Rehovot, Israël], Laboratoire de Biologie et de Pharmacologie Appliquée (LBPA), École normale supérieure - Cachan (ENS Cachan)-Centre National de la Recherche Scientifique (CNRS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon, Université Paris Diderot - Paris 7 (UPD7)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Université Paris Descartes - Paris 5 (UPD5)-Institut Curie-Institut National de la Santé et de la Recherche Médicale (INSERM), École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Weizmann Institute of Science |
| Rok vydání: | 2003 |
| Předmět: |
Small interfering RNA
Time Factors Transcription Genetic [SDV]Life Sciences [q-bio] Apoptosis Cell Cycle Proteins medicine.disease_cause S Phase Mice 0302 clinical medicine Transcription (biology) Tumor Cells Cultured Cloning Molecular Phosphorylation RNA Small Interfering Luciferases Promoter Regions Genetic Glutathione Transferase Oncogene Proteins 0303 health sciences Multidisciplinary Kinase Cell Cycle Cell cycle Protein-Tyrosine Kinases Biological Sciences Flow Cytometry Proto-Oncogene Proteins c-bcl-2 030220 oncology & carcinogenesis Oxidoreductases Protein Binding G2 Phase DNA Complementary Recombinant Fusion Proteins Blotting Western Molecular Sequence Data Mitosis [SDV.CAN]Life Sciences [q-bio]/Cancer [SDV.BC]Life Sciences [q-bio]/Cellular Biology Biology Protein Serine-Threonine Kinases Gene product 03 medical and health sciences Complementary DNA Proto-Oncogene Proteins Two-Hybrid System Techniques medicine Animals Humans Amino Acid Sequence RNA Messenger 030304 developmental biology [SDV.GEN]Life Sciences [q-bio]/Genetics Sequence Homology Amino Acid Tumor Suppressor Proteins G1 Phase Membrane Proteins Oligonucleotides Antisense Blotting Northern Molecular biology Precipitin Tests Protein Structure Tertiary Protein Biosynthesis Tumor Suppressor Protein p53 Carcinogenesis HeLa Cells |
| Zdroj: | Proceedings of the National Academy of Sciences of the United States of America Proceedings of the National Academy of Sciences of the United States of America, 2003, 100 (5), pp.2284-2289. ⟨10.1073/pnas.0530298100⟩ Proceedings of the National Academy of Sciences of the United States of America, National Academy of Sciences, 2003, 100 (5), pp.2284-2289. ⟨10.1073/pnas.0530298100⟩ |
| ISSN: | 0027-8424 1091-6490 |
| DOI: | 10.1073/pnas.0530298100⟩ |
| Popis: | The p53 tumor suppressor protein plays a crucial role in tumorigenesis by controlling cell-cycle progression and apoptosis. We have previously described a transcript designated tumor suppressor activated pathway-6 (TSAP6) that is up-regulated in the p53-inducible cell line, LTR6. Cloning of the murine and human full-length TSAP6 cDNA revealed that it encodes a 488-aa protein with five to six transmembrane domains. This gene is the murine and human homologue of the recently published rat pHyde. Antibodies raised against murine and human TSAP6 recognize a 50- to 55-kDa band induced by p53. Analysis of the TSAP6 promoter identified a functional p53-responsive element. Functional studies demonstrated that TSAP6 antisense cDNA diminished levels of the 50- to 55-kDa protein and decreased significantly the levels of p53-induced apoptosis. Furthermore, TSAP6 small interfering RNA inhibited apoptosis in TSAP6-overexpressing cells. Yeast two-hybrid analysis followed by GST/ in vitro -transcribed/translated pull-down assays and in vivo coimmunoprecipitations revealed that TSAP6 associated with Nix, a proapoptotic Bcl-2-related protein and the Myt1 kinase, a negative regulator of the G 2 /M transition. Moreover, TSAP6 enhanced the susceptibility of cells to apoptosis and cooperated with Nix to exacerbate this effect. Cell-cycle studies indicated that TSAP6 could augment Myt1 activity. Overall, these data suggest that TSAP6 may act downstream to p53 to interface apoptosis and cell-cycle progression. |
| Databáze: | OpenAIRE |
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