Reduction of Nup107 attenuates the growth factor signaling in the senescent cells.
Hypo-responsiveness to growth factors is a fundamental feature of cellular senescence. In this study, we found markedly decreased level of Nup107, a key scaffold protein in nuclear pore complex assembly, in senescent human diploid fibroblasts as well as in organs of aged mice. Depletion of Nup107 by specific siRNA in young human diploid fibroblasts prevented the effective nuclear translocation of phosphorylated extracellular signal-regulated kinase (ERK) following epidermal growth factor (EGF) stimulation, and decreased the expression of c-Fos in consequence. The disturbances in ERK signaling in Nup107 depleted cells closely mirror the similar changes in senescent cells. Knockdown of Nup107 in anaplastic oligodendroglioma cells caused cell death, rather than growth retardation, indicating a greater sensitivity to Nup107 depletion in cancer cells than in normal cells. These findings support the notion that Nup107 may contribute significantly to the regulation of cell fate in aged and transformed cells by modulating nuclear trafficking of signal molecules.
Kim
Sung Young
SY
Department of Biochemistry and Molecular Biology, Aging and Apoptosis Research Center, Seoul National University College of Medicine, Seoul 110-799, Republic of Korea.
Kang
Hyun Tae
HT
Choi
Hae Ri
HR
Park
Sang Chul
SC
D021581:Active Transport, Cell Nucleus / Q000187:drug effects; D000818:Animals; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D016922:Cellular Senescence; D002648:Child; D004815:Epidermal Growth Factor / Q000378:metabolism* / Q000494:pharmacology; D006801:Humans; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D028861:Nuclear Pore Complex Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D010766:Phosphorylation; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism; D015398:Signal Transduction; D019892:eIF-2 Kinase / Q000378:metabolism
D004815:Epidermal Growth Factor; D028861:Nuclear Pore Complex Proteins; D016760:Proto-Oncogene Proteins c-fos; D019892:eIF-2 Kinase; C512772:NUP107 protein, human