Silencing nuclear pore protein Tpr elicits a senescent-like phenotype in cancer cells.
basic_science · Level V
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- Record sourced from PubMed, PMID 21811608.
- Also identified by DOI 10.1371/journal.pone.0022423 and PMC identifier PMC1784014.
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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.