Inhibitor of apoptosis proteins are required for effective fusion of autophagosomes with lysosomes

Inhibitor of apoptosis proteins are required for effective fusion of autophagosomes with lysosomes

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...

Full description

Saved in:
Bibliographic Details
Published in:Cell death & disease 2018-05, Vol.9 (5), p.529-15, Article 529
Main Authors: Gradzka, Sylwia, Thomas, Oliver S, Kretz, Oliver, Haimovici, Aladin, Vasilikos, Lazaros, Wong, Wendy Wei-Lynn, Häcker, Georg, Gentle, Ian E
Format: Article
Language:eng
Subjects:
Apoptosis
Autophagy
IAP protein
Lymphocytes
Lysosomes
Mutation
NF-κB protein
NOD2 protein
Pattern recognition
Phagocytosis
Phagosomes
Proteins
Tumor necrosis factor
Tumor necrosis factor receptors
Ubiquitin
XIAP protein
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary: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.
ISSN:2041-4889
2041-4889