Εξειδίκευση τύπου :	Άρθρο σε επιστημονικό περιοδικό
Τίτλος:	FoxO1 Is a novel regulator of 20S proteasome subunits expression and activity
Δημιουργός/Συγγραφέας:	Kapetanou, Marianna Nespital, Tobias Tain, Luke S Pahl, Andre Partridge, Linda [EL] Γκόνος, Ευστάθιος[EN] Gonos, Efstathios S.
Εκδότης:	Frontiers Media
Ημερομηνία:	2021
Γλώσσα:	Αγγλικά
ISSN:	2296-634X
DOI:	10.3389/fcell.2021.625715
Άλλο:	33634126
Περίληψη:	Proteostasis collapses during aging resulting, among other things, in the accumulation of damaged and aggregated proteins. The proteasome is the main cellular proteolytic system and plays a fundamental role in the maintenance of protein homeostasis. Our previous work has demonstrated that senescence and aging are related to a decline in proteasome content and activities, while its activation extends lifespan in vitro and in vivo in various species. However, the mechanisms underlying this age-related decline of proteasome function and the down-regulation in expression of its subunits remain largely unclear. Here, we demonstrate that the Forkhead box-O1 (FoxO1) transcription factor directly regulates the expression of a 20S proteasome catalytic subunit and, hence, proteasome activity. Specifically, we demonstrate that knockout of FoxO1, but not of FoxO3, in mice severely impairs proteasome activity in several tissues, while depletion of IRS1 enhances proteasome function. Importantly, we show that FoxO1 directly binds on the promoter region of the rate-limiting catalytic β5 proteasome subunit to regulate its expression. In summary, this study reveals the direct role of FoxO factors in the regulation of proteasome function and provides new insight into how FoxOs affect proteostasis and, in turn, longevity.
Τίτλος πηγής δημοσίευσης:	Frontiers in cell and developmental biology
Τόμος/Κεφάλαιο:	9
Σελίδες:	625715
Θεματική Κατηγορία:	[EL] Βιοχημεία[EN] Biochemistry [EL] Κυτταρολογία[EN] Cytology
Λέξεις-Κλειδιά:	FOXO factors Aging Insulin signaling Longevity Proteasome Proteostasis
Κάτοχος πνευματικών δικαιωμάτων:	Copyright © 2021 by the Authors
Ηλεκτρονική διεύθυνση στον εκδότη (link):	https://www.frontiersin.org/articles/10.3389/fcell.2021.625715/full
Ηλεκτρονική διεύθυνση περιοδικού (link) :	https://www.frontiersin.org/journals/cell-and-developmental-biology
Εμφανίζεται στις συλλογές:	Ινστιτούτο Χημικής Βιολογίας - Επιστημονικό έργο