Εξειδίκευση τύπου :	Άρθρο σε επιστημονικό περιοδικό
Τίτλος:	Partial proteasome inhibition in human fibroblasts triggers accelerated M1 senescence or M2 crisis depending on p53 and Rb status
Δημιουργός/Συγγραφέας:	[EL] Χονδρογιάννη, Νίκη[EN] Chondrogianni, Niki [EL] Τρουγκάκος, Ιωάννης Π.[EN] Trougakos, Ioannis P. Kletsas, Dimitris Chen, Qin M. [EL] Γκόνος, Ευστάθιος[EN] Gonos, Efstathios S.
Εκδότης:	Wiley-blackwell
Τόπος έκδοσης:	Malden
Ημερομηνία:	2008-10
Γλώσσα:	Αγγλικά
ISSN:	1474-9718
DOI:	10.1111/j.1474-9726.2008.00425.x
Περίληψη:	Proteasome-dependent degradation has been extensively investigated and has been shown to play a vital role in the maintenance of cellular homeostasis. Proteasome activity and expression are reduced during aging and replicative senescence. Its activation has been shown to confer lifespan extension in human diploid fibroblasts (HDFs), whereas partial proteasome inhibition triggers an irreversible premature senescent state in young HDFs. As p53 and Rb tumor suppressors regulate both replicative and premature senescence (RS and PS, respectively), in this study we investigated their implication in proteasome inhibition-mediated PS. By taking advantage of a variety of HDFs with defective p53 or/and Rb pathways, we reveal that proteasome activity inhibition to levels normally found in senescent human cells results in immediate growth arrest and/or moderate increase of apoptotic death. These effects are independent of the cellular genetic context. However, in the long term, proteasome inhibition-mediated PS can only be initiated and maintained in the presence of functional p53. More specifically, we demonstrate that following partial proteasome inhibition, senescence is dominant in HDFs with functional p53 and Rb molecules, crisis/death is induced in cells with high p53 levels and defective Rb pathway, whereas stress recovery and restoration of normal cycling occurs in cells that lack functional p53. These data reveal the continuous interplay between the integrity of proteasome function, senescence and cell survival.
Τίτλος πηγής δημοσίευσης:	Aging Cell
Τόμος/Κεφάλαιο:	7
Τεύχος:	5
Σελίδες:	717-732
Θεματική Κατηγορία:	[EL] Βιολογία (Γενικά)[EN] Biology (General)
Λέξεις-Κλειδιά:	aging premature senescence proteasome proteasome inhibition p53 Rb Geriatrics & Gerontology
Αξιολόγηση από ομότιμους (peer reviewed):	Ναι
Όροι και προϋποθέσεις δικαιωμάτων:	This is an open access Journal. This article appears in: "Aging Cell (2008), v7, issue5 717-732" and can be found at the following URL: http://dx.doi.org/10.1111/j.1474-9726.2008.00425.x
Ηλεκτρονική διεύθυνση περιοδικού (link) :	https://onlinelibrary.wiley.com/journal/14749726
ΙΒΦΧΒ: αρχειακή συλλογή:	Ινστιτούτο Βιολογικών Ερευνών και Βιοτεχνολογίας (ΙΒΕΒ) (έως 2012)
Εμφανίζεται στις συλλογές:	Ινστιτούτο Χημικής Βιολογίας - Επιστημονικό έργο