title: Silencing nuclear pore protein Tpr elicits a senescent-like phenotype in cancer cells.
abstract: BACKGROUND
  Tpr is a large coiled-coil protein located in the nuclear basket of the nuclear pore complex for which many different functions were proposed from yeast to human.
  
  
  RESULTS
  Here we show that depletion of Tpr by RNA interference triggers G0-G1 arrest and ultimately induces a senescent-like phenotype dependent on the presence of p53. We also found that Tpr depletion impairs the NES [nuclear export sequence]-dependent nuclear export of proteins and causes partial co-depletion of Nup153. In addition Tpr depletion impacts on level and function of the SUMO-protease SENP2 thus affecting SUMOylation regulation at the nuclear pore and overall SUMOylation in the cell.
  
  
  CONCLUSIONS
  Our data for the first time provide evidence that a nuclear pore component plays a role in controlling cellular senescence. Our findings also point to new roles for Tpr in the regulation of SUMO-1 conjugation at the nuclear pore and directly confirm Tpr involvement in the nuclear export of NES-proteins.
authors.affiliation: Institut Pasteur, CNRS URA2582, Groupe E3 Biologie Cellulaire du Noyau, Paris, France. brigitte.david-watine@pasteur.fr
authors.forename: Brigitte
authors.initials: B
authors.lastname: David-Watine
mesh_terms: D021581:Active Transport, Cell Nucleus; D016922:Cellular Senescence; D003546:Cysteine Endopeptidases / Q000378:metabolism; D016193:G1 Phase; D017353:Gene Deletion; D055785:Gene Knockdown Techniques; D020868:Gene Silencing; D006367:HeLa Cells; D006801:Humans; D028884:Karyopherins / Q000378:metabolism; D049790:Nuclear Export Signals; D022022:Nuclear Pore / Q000378:metabolism*; D028861:Nuclear Pore Complex Proteins / Q000378:metabolism*; D010641:Phenotype; D011518:Proto-Oncogene Proteins / Q000378:metabolism*; D018160:Receptors, Cytoplasmic and Nuclear / Q000378:metabolism; D016192:Resting Phase, Cell Cycle; D025841:Small Ubiquitin-Related Modifier Proteins / Q000378:metabolism; D058207:Sumoylation; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism; D000097606:Exportin 1 Protein
chemical_list: D003546:Cysteine Endopeptidases; D028884:Karyopherins; D049790:Nuclear Export Signals; D028861:Nuclear Pore Complex Proteins; D011518:Proto-Oncogene Proteins; D018160:Receptors, Cytoplasmic and Nuclear; D025841:Small Ubiquitin-Related Modifier Proteins; D016159:Tumor Suppressor Protein p53; D000097606:Exportin 1 Protein; C079377:NUP153 protein, human; C073597:TPR protein, human; C501833:SENP2 protein, human