AMBRA1 phosphorylation by CDK1 and PLK1 regulates mitotic spindle orientation

Fiorella Faienza, Federica Polverino, Girish Rajendraprasad, Giacomo Milletti, Zehan Hu, Barbara Colella, Deborah Gargano, Flavie Strappazzon, Salvatore Rizza, Mette Vixø Vistesen, Yonglun Luo, Manuela Antonioli, Valentina Cianfanelli, Caterina Ferraina, Gian Maria Fimia, Giuseppe Filomeni, Daniela De Zio, Joern Dengjel, Marin Barisic, Giulia GuarguagliniSabrina Di Bartolomeo, Francesco Cecconi*

*Corresponding author for this work

Research output: Contribution to journalJournal articleResearchpeer-review

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Abstract

AMBRA1 is a crucial factor for nervous system development, and its function has been mainly associated with autophagy. It has been also linked to cell proliferation control, through its ability to regulate c-Myc and D-type cyclins protein levels, thus regulating G1-S transition. However, it remains still unknown whether AMBRA1 is differentially regulated during the cell cycle, and if this pro-autophagy protein exerts a direct role in controlling mitosis too. Here we show that AMBRA1 is phosphorylated during mitosis on multiple sites by CDK1 and PLK1, two mitotic kinases. Moreover, we demonstrate that AMBRA1 phosphorylation at mitosis is required for a proper spindle function and orientation, driven by NUMA1 protein. Indeed, we show that the localization and/or dynamics of NUMA1 are strictly dependent on AMBRA1 presence, phosphorylation and binding ability. Since spindle orientation is critical for tissue morphogenesis and differentiation, our findings could account for an additional role of AMBRA1 in development and cancer ontogenesis.

Original languageEnglish
Article number251
JournalCellular and Molecular Life Sciences
Volume80
Issue number9
ISSN1420-682X
DOIs
Publication statusPublished - 2023

Bibliographical note

Publisher Copyright:
© 2023, The Author(s).

Keywords

  • Cell cycle
  • Mitotic kinases
  • Mitotic spindle
  • NUMA1
  • Phosphorylation

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