CCDC115 inhibits autophagy-mediated degradation of YAP to promote cell proliferation.

Autophagy and Hippo signaling pathways both play important roles in cell homeostasis and are often involved in tumorigenesis. However, the crosstalk between these two signal pathways in response to stress conditions, such as nutrient deficiency, is incompletely understood. Here, we show that vesicular localized coiled-coil domain containing 115 (CCDC115) inhibits autophagy as well as Hippo signaling pathway under starvation. Moreover, we show that CCDC115 interacts with the HOPS complex. This interaction competes with STX17, thus inhibiting the fusion of autophagosomes with lysosomes. Hence, CCDC115 inhibits the autophagic degradation of yes-associated protein (YAP), thereby promoting cell proliferation in nutrient-restricted situation.