Autophagy In Cell Cycle Regulation

Autophagy, a highly conserved catabolic process in eukaryotic cells, is a lysosome-dependent degradation pathway implicated in various physiological and pathological processes. Emerging studies have demonstrated that autophagy suppresses carcinogenesis by limiting genomic instability, while the underlying molecular mechanism remains elusive. Accurate cell cycle regulation is required for the maintenance of genomic stability during cell proliferation. However, little is known about the relevance between autophagy and cell cycle regulation. Here, we found that deficiency of autophagy induced cell G2/M phase arrest, leading to M phase delay and cell multinucleation. The expression of mRNA of PLK4, a member of polo-like kinase family, was decreased in autophagy deficient cells. Further analysis demonstrated that overexpression of p62, an adaptor protein required for autophagy and itself is degraded by autophagy, reduced mRNA level of PLK4. Our results suggest an important role of autophagy in cell cycle regulation. The suppression of PLK4expression caused by p62accumulation may be causally linked with the cell cycle disorder, which could represent a possible mechanism for genomic instability induced by autophagy disruption.