Inhibitor of apoptosis proteins are required for effective fusion of autophagosomes with lysosomes.
Cell Death Dis
; 9(5): 529, 2018 05 01.
Article
em En
| MEDLINE
| ID: mdl-29743550
ABSTRACT
Inhibitor of Apoptosis Proteins act as E3 ubiquitin ligases to regulate NF-κB signalling from multiple pattern recognition receptors including NOD2, as well as TNF Receptor Superfamily members. Loss of XIAP in humans causes X-linked Lymphoproliferative disease type 2 (XLP-2) and is often associated with Crohn's disease. Crohn's disease is also caused by mutations in the gene encoding NOD2 but the mechanisms behind Crohn's disease development in XIAP and NOD2 deficient-patients are still unknown. Numerous other mutations causing Crohn's Disease occur in genes controlling various aspects of autophagy, suggesting a strong involvement of autophagy in preventing Crohn's disease. Here we show that the IAP proteins cIAP2 and XIAP are required for efficient fusion of lysosomes with autophagosomes. IAP inhibition or loss of both cIAP2 and XIAP resulted in a strong blockage in autophagic flux and mitophagy, suggesting that XIAP deficiency may also drive Crohn's Disease due to defects in autophagy.
Texto completo:
1
Coleções:
01-internacional
Temas:
Geral
Base de dados:
MEDLINE
Assunto principal:
Doença de Crohn
/
Proteínas Inibidoras de Apoptose
/
Mitofagia
/
Autofagossomos
/
Proteína 3 com Repetições IAP de Baculovírus
/
Lisossomos
/
Fusão de Membrana
Limite:
Animals
Idioma:
En
Revista:
Cell Death Dis
Ano de publicação:
2018
Tipo de documento:
Article
País de afiliação:
Alemanha