Survive or thrive: tradeoff strategy for cellular senescence
Experimental & Molecular Medicine
;
: e342-2017.
Article
Dans Anglais
| WPRIM
| ID: wpr-161484
ABSTRACT
Aging-dependent cellular behaviors toward extrinsic stress are characterized by the confined localization of certain molecules to either nuclear or perinuclear regions. Although most growth factors can activate downstream signaling in aging cells, they do not in fact have any impact on the cells because the signals cannot reach their genetic targets in the nucleus. For the same reason, varying apoptotic stress factors cannot stimulate the apoptotic pathway in senescent cells. Thus, the operation of a functional nuclear barrier in an aging-dependent manner has been investigated. To elucidate the mechanism for this process, the housekeeping transcription factor Sp1 was identified as a general regulator of nucleocytoplasmic trafficking (NCT) genes, including various nucleoporins, importins, exportins and Ran GTPase cycle-related genes. Interestingly, the posttranslational modification of Sp1 is readily influenced by extrinsic stress, including oxidative and metabolic stress. The decrease in SP1 O-GlcNAcylation under oxidative stress or during replicative senescence makes it susceptible to proteosomal degradation, resulting in defective NCT functions and leading to nuclear barrier formation. The operation of the nuclear barrier in aging provides a fundamental mechanism for cellular protection against stress and promotes survival at the expense of growth via stress-sensitive transcriptional control.
Texte intégral:
Disponible
Indice:
WPRIM (Pacifique occidental)
Sujet Principal:
Stress physiologique
/
Facteurs de transcription
/
Vieillissement
/
Maturation post-traductionnelle des protéines
/
Vieillissement de la cellule
/
Stress oxydatif
/
Caryophérines
/
Complexe protéique du pore nucléaire
/
Protéines et peptides de signalisation intercellulaire
/
DGTPases
Type d'étude:
Étude pronostique
langue:
Anglais
Texte intégral:
Experimental & Molecular Medicine
Année:
2017
Type:
Article
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