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Significance The Hippo signaling pathway is evolutionarily conserved in the animal kingdom and plays essential roles in regulating tissue growth during development and regeneration. We have identified APC/CCdh1 , a core component of cell cycle control machinery, as an evolutionarily conserved and previously unknown regulator of large tumor suppressor (LATS) kinases, which critically inhibit the YAP/TAZ transcription factors in transducing Hippo signaling. Our results suggest a model that APC/CCdh1 destabilizes LATS1/2 kinases in G1 phase of the cell cycle, leading to increased YAP/TAZ activities that promote G1/S transition by upregulating downstream gene expression, includingE2F1 . Our findings have important implications for a link between cell proliferation and LATS-regulated YAP/TAZ activities.

Hippo signaling is intrinsically regulated during cell cycle progression by APC/C Cdh1

Hippo signaling is intrinsically regulated during cell cycle progression by APC/C ^Cdh1