INVESTIGATION OF THE ROLE OF CUL4-RING UBIQUITIN LIGASES IN AUTOPHAGY DURING MITOSIS

Abstract

Autophagy is a cellular process in which cytosolic contents are degraded by lysosome in response to various stress conditions. So far, whether and how autophagy is regulated by cell cycle especially during mitosis remains largely undefined. Here we show that upon mitosis induction, CRL4s are activated via neddylation, leading to WIPI2 poly-ubiquitination and proteasomal degradation and suppression of autophagy. Furthermore, mitotic suppression of autophagy could be rescued by MLN4924, which leads to mitotic slippage and cell senescence. Our study thus discovers a novel function of CRL4s in autophagy by targeting WIPI2 for polyubiquitination and proteasomal degradation during mitosis.