The anaphase promoting complex induces substrate degradation during neuronal differentiation

Abstract

The anaphase promoting complex (APC) is an E3 ubiquitin ligase required for the metaphase-to-anaphase transition and mitotic exit. However, APC also plays roles in G1, where it is regulated by Cdh1, and APC activity has also been detected in differentiated and non-proliferating cells, suggesting that it may play roles outside the cell cycle. Here, we report that disrupting APCCdh1 activity inhibits neurite outgrowth of both PC12 pheochromocytoma cells and primary cerebellar granule cells. APCCdh1 activity dramatically increases as PC12 cells differentiate in response to nerve growth factor. Furthermore, a key target degraded by APCCdh1 following nerve growth factor treatment is the F-box protein Skp2, and APCCdh1-mediated destruction of Skp2 is essential for proper terminal differentiation of neuronal precursors. © 2009 by The American Society for Biochemistry and Molecular Biology, Inc.