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- ¿¬ Á¦ : Cause of Cellular Senescence: Impairment of nucleocytoplasmic trafficking
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Cause of Cellular Senescence: Impairment of nucleocytoplasmic trafficking
Young-Sam Lee
Department of New Biology, DGIST, Daegu 42988, Korea
Abstract
Senescent cells acquire resistance not only to apoptotic stimuli but also to mitogenic signals. It has
been shown that such resistance can be mediated by disrupted transmission of apoptotic and
mitogenic signals between the cytoplasm and nucleus. Proteomic and transcriptomic analyses
apparently illustrate the differences in distribution of proteins and RNAs between cytoplasm and
nucleus of young and senescent cells. These data implicate the blocking of nucleocytoplasmic
trafficking (NCT) as an intrinsic attribute of replicative senescence (RS). It is intriguing to test
whether the impairment of NCT, named ¡°nuclear barrier formation¡± can cause cellular senescence.
We discovered that nuclear barrier induction by blocking NCT, particularly nuclear export, leads to
RS-like changes. Thereby, a new modality of senescence induction has been designated as nuclear
barrier-induced senescence (NBIS). Further comparative transcriptome analysis revealed that NBIS
is very similar in gene expression changes to RS, compared to other modes of stress-induced
senescence. These results indicate that NBIS might be deeply relevant to replicative senescence.
Their sharing common features in lysosomal degradation, nuclear transport, and translation lead to
coordinated reduction in transmission of signals of proteins and RNAs to and from the nucleus in
senescence. This nature of NCT is confirmed to be conserved in yeast aging as well, suggesting the
evolutionary origin of senescence. Taken together, it can be concluded that NBIS is a novel modality
of cellular senescence and represents the fundamental nature of physiological aging of eukaryotes.