c-FLIP regulates autophagy by interacting with Beclin-1 and influencing its stability.
Cell Death Dis
; 12(7): 686, 2021 07 08.
Article
em En
| MEDLINE
| ID: mdl-34238932
ABSTRACT
c-FLIP (cellular FLICE-like inhibitory protein) protein is mostly known as an apoptosis modulator. However, increasing data underline that c-FLIP plays multiple roles in cellular homoeostasis, influencing differently the same pathways depending on its expression level and isoform predominance. Few and controversial data are available regarding c-FLIP function in autophagy. Here we show that autophagic flux is less effective in c-FLIP-/- than in WT MEFs (mouse embryonic fibroblasts). Indeed, we show that the absence of c-FLIP compromises the expression levels of pivotal factors in the generation of autophagosomes. In line with the role of c-FLIP as a scaffold protein, we found that c-FLIPL interacts with Beclin-1 (BECN1 coiled-coil, moesin-like BCL2-interacting protein), which is required for autophagosome nucleation. By a combination of bioinformatics tools and biochemistry assays, we demonstrate that c-FLIPL interaction with Beclin-1 is important to prevent Beclin-1 ubiquitination and degradation through the proteasomal pathway. Taken together, our data describe a novel molecular mechanism through which c-FLIPL positively regulates autophagy, by enhancing Beclin-1 protein stability.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Autofagia
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Proteína Reguladora de Apoptosis Semelhante a CASP8 e FADD
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Fibroblastos
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Proteína Beclina-1
Limite:
Animals
/
Humans
Idioma:
En
Revista:
Cell Death Dis
Ano de publicação:
2021
Tipo de documento:
Article
País de afiliação:
Itália