UBAP2L ‐dependent coupling of PLK1 localization and stability during mitosis

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

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

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.

Mots clés: PLK1; UBAP2L; Mitosis

Domaines: Sciences du Vivant [q-bio]

Lucile Guerber, Aurore Vuidel, Yongrong Liao, Charlotte Kleiss, Erwan Grandgirard, et al.. UBAP2L ‐dependent coupling of PLK1 localization and stability during mitosis. EMBO Reports, 2023, 24 (6), ⟨10.15252/embr.202256241⟩. ⟨hal-04247562⟩