Εξειδίκευση τύπου :	Άρθρο σε επιστημονικό περιοδικό
Τίτλος:	CHIP-dependent p53 regulation occurs specifically during cellular senescence
Δημιουργός/Συγγραφέας:	Sisoula, Christina Trachana, Varvara Patterson, Cam [EL] Γκόνος, Ευστάθιος[EN] Gonos, Efstathios S.
Εκδότης:	Elsevier Inc.
Τόπος έκδοσης:	NEW YORK
Ημερομηνία:	2011-01-01
Γλώσσα:	Αγγλικά
ISSN:	0891-5849
DOI:	10.1016/j.freeradbiomed.2010.10.701
Περίληψη:	p53 regulates several biological processes, including senescence. Its protein stability is regulated by ubiquitination and proteasomal degradation, mainly mediated by Mdm2. However, other E3 ligases have been identified, such as the chaperone-associated ligase CHIP, although their precise function regarding p53 degradation remains elusive. Interestingly, CHIP deficiency has been recently shown to result in accelerated aging in mice, although the molecular basis of this phenotype was not completely understood. In this study, we explore the role of CHIP in regulating p53 in senescence. We demonstrate that in senescent human fibroblasts, CHIP is up-regulated concomitant with a significant down-regulation of p53. Moreover, CHIP partially translocates to the nucleus and acquires higher ubiquitination levels in senescent cells. Notably, CHIP overexpression in young cells, to levels similar to those recorded during senescence, leads to p53 degradation to below its basal levels. In addition, whereas CHIP silencing has no effect on p53 stability in young cells, a considerable p53 accumulation occurs in their senescent counterparts. Finally, we have observed an attenuation of the CHIP-associated molecular folding-refolding machinery during senescence, and supportively, inhibition of Hsp90 activity leads to rapid p53 degradation only in senescent cells. Taking these results together, we conclude that CHIP-dependent p53 regulation occurs specifically during senescence.
Τίτλος πηγής δημοσίευσης:	Free Radical Biology and Medicine (incorporating Advances in Free Radical Biology & Medicine and Journal of Free Radicals in Biology & Medicine)
Τόμος/Κεφάλαιο:	50
Τεύχος:	1
Σελίδες:	157-165
Θεματική Κατηγορία:	[EL] Βιολογία (Γενικά)[EN] Biology (General) [EL] Εσωτερική ιατρική[EN] Internal medicine
Λέξεις-Κλειδιά:	CHIP ligase Degradation p53 Replicative senescence Ubiquitin-proteasome system Aging Free radicals Endocrinology & Metabolism
Αξιολόγηση από ομότιμους (peer reviewed):	Ναι
Κάτοχος πνευματικών δικαιωμάτων:	© 2010 Elsevier Inc. All rights reserved.
Ηλεκτρονική διεύθυνση περιοδικού (link) :	http://www.elsevier.com/locate/freeradbiomed
ΙΒΦΧΒ: αρχειακή συλλογή:	Ινστιτούτο Βιολογικών Ερευνών και Βιοτεχνολογίας (ΙΒΕΒ) (έως 2012)
Εμφανίζεται στις συλλογές:	Ινστιτούτο Χημικής Βιολογίας - Επιστημονικό έργο