UBAP2L ‐dependent coupling of PLK1 localization and stability during mitosis

Abstract

PLK1 is an important regulator of mitosis whose protein levels and activity fluctuate during the cell cycle. PLK1 dynamically localizes to various mitotic structures to regulate chromosome segregation. However, the signaling pathways linking localized PLK1 activity to its protein stability remain elusive. Here, we identify the Ubiquitin‐Binding Protein 2‐Like (UBAP2L) that controls both the localization and the protein stability of PLK1. We demonstrate that UBAP2L is a spindle‐associated protein whose depletion leads to severe mitotic defects. UBAP2L‐depleted cells are characterized by increased PLK1 protein levels and abnormal PLK1 accumulation in several mitotic structures such as kinetochores, centrosomes and mitotic spindle. UBAP2L‐deficient cells exit mitosis and enter the next interphase in the presence of aberrant PLK1 kinase activity. The C‐terminal domain of UBAP2L mediates its function on PLK1 independently of its role in stress response signaling. Importantly, the mitotic defects of UBAP2L‐depleted cells are largely rescued by chemical inhibition of PLK1. Overall, our data suggest that UBAP2L is required to fine‐tune the ubiquitin‐mediated PLK1 turnover during mitosis as a means to maintain genome fidelity. image UBAP2L directly regulates the global turnover of PLK1 during mitotic progression and is essential for the fidelity of chromosome segregation. UBAP2L ensures proper chromosome segregation during mitosis. UBAP2L‐mediated regulation of PLK1 is independent of stress signaling. UBAP2L controls both PLK1 stability and localization during mitotic progression. Restoration of PLK1 signaling rescues the segregation errors in UBAP2L‐deficient cells.