AMBRA1 phosphorylation by CDK1 and PLK1 regulates mitotic spindle orientation

• DOI: 10.1007/s00018-023-04878-6
• Publication Date: 2023-08-16T15:01:43Z
• Authors: Fiorella Faienza; Federica Polverino; Girish Rajendrapr...; Giacomo Milletti; Zehan Hu; Barbara Colella; Deborah Gargano; Flavie Strappazzon; Salvatore Rizza; Mette Vixø Vistesen; Yonglun Luo; Manuela Antonioli; Valentina Cianfan...; Caterina Ferraina; Gian Maria Fimia; Giuseppe Filomeni; Daniela De Zio; Joern Dengjel; Marin Barisic; Giulia Guarguaglini; Sabrina Di Bartol...; Francesco Cecconi
• Keywords: PLK1

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