UBAP2L-dependent coupling of PLK1 localization and stability during mitosis

Lucile Guerber (1) , Evanthia Pangou (1) , Aurore Vuidel (1) , Yongrong Liao (1) , Charlotte Kleiss (1) , Erwan Grandgirard (1) , Izabela Sumara (1)

1 IGBMC - Institut de Génétique et de Biologie Moléculaire et Cellulaire

Abstract PLK1 is a key regulator of mitosis whose protein levels and activity fluctuate during cell cycle. PLK1 dynamically localizes to distinct mitotic structures to regulate proper chromosome segregation. However, the molecular mechanisms linking localized PLK1 activity to its protein stability remain elusive. Here, we identify the Ubiquitin-Binding Protein 2-Like (UBAP2L) protein that regulates both dynamic removal of PLK1 from kinetochores and PLK1 protein stability during mitosis. We demonstrate that UBAP2L localizes to kinetochores in a PLK1-dependent manner and that UBAP2L depletion leads to the abnormal retention of PLK1 at kinetochores and segregation defects. We show that C-terminal domain of UBAP2L mediates its function on PLK1 and that UBAP2L specifically regulates PLK1 and no other mitotic factors. We demonstrate that inhibited kinetochore removal of PLK1 in UBAP2L-depleted cells, increases PLK1 stability after mitosis completion and results in aberrant PLK1 kinase activity in interphase and cellular death. Overall, our data suggest that UBAP2L is required to fine-tune PLK1 signaling in human cells. Graphical Abstract

Domaines: Sciences du Vivant [q-bio]

Lucile Guerber, Evanthia Pangou, Aurore Vuidel, Yongrong Liao, Charlotte Kleiss, et al.. UBAP2L-dependent coupling of PLK1 localization and stability during mitosis. 2022. ⟨hal-03869696⟩