silencing nuclear pore protein tpr elicits a senescent-like phenotype in cancer cells沉默核孔蛋白tpr抒发senescent-like癌症细胞的表型.pdfVIP

Silencing Nuclear Pore Protein Tpr Elicits a Senescent- Like Phenotype in Cancer Cells Brigitte David-Watine* Institut Pasteur, CNRS URA2582, Groupe E3 Biologie Cellulaire du Noyau, Paris, France 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. Methodology/Principal Findings: 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. Citation: David-Watine B (2011) Silencing Nuclear Pore Protein Tpr Elicits a Senescent-Like Phenotype in Cancer Cells. PLoS ONE 6(7): e22423. doi:10.1371/ journal.pone.0022423 Editor: Michael Polymenis, Texas AM University, United States of America Received April 1, 2011; Accepted June 22, 2011; Published July 19, 2011 Copyright: 2011 Brigitte David-Watine. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Funding: This work