Abstract
BackgroundTpr 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 FindingsHere 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.ConclusionsOur 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.
Highlights
Nuclear pore complexes (NPCs) mediate all selective bidirectional transport between the nucleus and the cytoplasm
Our data for the first time provide evidence that a nuclear pore component plays a role in controlling cellular senescence
Our findings 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 nuclear export sequence (NES)-proteins
Summary
Nuclear pore complexes (NPCs) mediate all selective bidirectional transport between the nucleus and the cytoplasm. The protein Tpr (for translocated promoter region) and its homologues are a conserved component at the nuclear side of NPC. Many functions have been attributed to Tpr and its homologues in different species in addition to a role in NPC architecture. These include mRNA export control [9,10], nuclear protein export [4,11], silent telomeric chromatin organization and telomere length control [12,13,14]. 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
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