Autophagy-mediated degradation of nuclear envelope proteins during oncogene-induced senescence.

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Serval ID
serval:BIB_52D9B372ED95
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Autophagy-mediated degradation of nuclear envelope proteins during oncogene-induced senescence.
Journal
Carcinogenesis
Author(s)
Lenain C., Gusyatiner O., Douma S., van den Broek B., Peeper D.S.
ISSN
1460-2180 (Electronic)
ISSN-L
0143-3334
Publication state
Published
Issued date
2015
Peer-reviewed
Oui
Volume
36
Number
11
Pages
1263-1274
Language
english
Abstract
Cellular senescence is a largely irreversible form of cell cycle arrest triggered by various types of damage and stress, including oncogene expression (termed oncogene-induced senescence or OIS). We and others have previously demonstrated that OIS occurs in human benign lesions, acting as a potent tumor suppressor mechanism. Numerous phenotypic changes occur during OIS, both in the cytoplasm and in the nucleus. These include the activation of autophagy, a catabolic process operating in the cytoplasm and downregulation of lamin B1, a component of the nuclear lamina. However, it is unknown whether these changes relate to each other. We discovered that cells entering BRAF(V600E)- or H-RAS(G12V)-induced senescence downregulate not only lamin B1 but also lamin A, as well as several other nuclear envelope (NE) proteins, resulting in an altered NE morphology. Depletion of LMNB1 or LMNA/C was sufficient to recapitulate some OIS features, including cell cycle exit and downregulation of NE proteins. We further found that the global loss of NE proteins is a consequence of their degradation by the autophagy machinery, which occurs concomitantly with autophagy induction and increased lysosomal content and activity. Our study therefore reveals a previously unknown connection between autophagy and the disruption of NE integrity during OIS.
Keywords
Autophagy, Cell Aging, Cell Line, Cell Nucleus Shape, Humans, Nuclear Envelope/metabolism, Nuclear Proteins/metabolism, Oncogenes, Proteolysis
Pubmed
Open Access
Yes
Create date
16/02/2016 17:46
Last modification date
25/09/2019 6:09
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