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Silencing Nuclear Pore Protein Tpr Elicits a Senescent-Like Phenotype in Cancer Cells
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 i...
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Public Library of Science
2011
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3139644/ https://www.ncbi.nlm.nih.gov/pubmed/21811608 http://dx.doi.org/10.1371/journal.pone.0022423 |
Sumario: | 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. |
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