Inhibitor of apoptosis proteins are required for effective fusion of autophagosomes with lysosomes
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Inhibitor of apoptosis proteins are required for effective fusion of autophagosomes with lysosomes. / Gradzka, Sylwia; Thomas, Oliver S; Kretz, Oliver; Haimovici, Aladin; Vasilikos, Lazaros; Wong, Wendy Wei-Lynn; Häcker, Georg; Gentle, Ian E.
in: CELL DEATH DIS, Jahrgang 9, 01.05.2018, S. 529.Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung
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TY - JOUR
T1 - Inhibitor of apoptosis proteins are required for effective fusion of autophagosomes with lysosomes
AU - Gradzka, Sylwia
AU - Thomas, Oliver S
AU - Kretz, Oliver
AU - Haimovici, Aladin
AU - Vasilikos, Lazaros
AU - Wong, Wendy Wei-Lynn
AU - Häcker, Georg
AU - Gentle, Ian E
PY - 2018/5/1
Y1 - 2018/5/1
N2 - 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.
AB - 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.
KW - Journal Article
U2 - 10.1038/s41419-018-0508-y
DO - 10.1038/s41419-018-0508-y
M3 - SCORING: Journal article
C2 - 29743550
VL - 9
SP - 529
JO - CELL DEATH DIS
JF - CELL DEATH DIS
SN - 2041-4889
ER -