PT  - JOURNAL ARTICLE
AU  - Poetsch, Isabella
AU  - Ebner, Petra
AU  - Deszcz, Luiza
AU  - Bachtrog, Iris
AU  - Stephani, Madlen
AU  - Díaz, Carlos Gómez
AU  - Dagdas, Yasin
AU  - Ikeda, Fumiyo
TI  - The anti-apoptosis ubiquitin E3 ligase XIAP promotes autophagosome-lysosome fusion during autophagy
AID  - 10.1101/291294
DP  - 2018 Jan 01
TA  - bioRxiv
PG  - 291294
4099  - http://biorxiv.org/content/early/2018/03/29/291294.short
4100  - http://biorxiv.org/content/early/2018/03/29/291294.full
AB  - The Inhibitor of Apoptosis Protein (IAP) family members are well-known endogenous regulators of apoptosis. Whether these proteins regulate other degradation pathways is unclear. Here, we discovered that the IAP member X-linked IAP (XIAP) is crucial for macroautophagy. Loss of XIAP in mouse and human cells inhibited starvation-induced degradation of LC3 proteins and an autophagy substrate p62. It also led to the accumulation of mature autophagosomes, suggesting that XIAP controls autophagic flux by mediating autolysosome formation. Xiap∆RING/∆RING cells phenocopy the autophagy defects of Xiap−/− cells, suggesting that the ubiquitinating activity mediated by the catalytic RING domain is critical for autophagic flux. We found that XIAP physically interacts with Syntaxin 17, a regulator of autophagosome-lysosome fusion. Syntaxin 17-positive mature autophagosomes positive accumulate in the cytoplasm of starved Xiap−/− cells, suggesting that XIAP might regulate its dissociation from autophagosomes after fusion. XIAP selectively interacts with GABARAP among LC3 family members via the LIR-Docking Site (LDS). Together, our data suggest that XIAP-mediated ubiquitination regulates key autophagy regulators to promote autophagosome-lysosome fusion.