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AMBRA1 phosphorylation by CDK1 and PLK1 regulates mitotic spindle orientation.

Authors :
Faienza, Fiorella
Polverino, Federica
Rajendraprasad, Girish
Milletti, Giacomo
Hu, Zehan
Colella, Barbara
Gargano, Deborah
Strappazzon, Flavie
Rizza, Salvatore
Vistesen, Mette Vixø
Luo, Yonglun
Antonioli, Manuela
Cianfanelli, Valentina
Ferraina, Caterina
Fimia, Gian Maria
Filomeni, Giuseppe
De Zio, Daniela
Dengjel, Joern
Barisic, Marin
Guarguaglini, Giulia
Source :
Cellular & Molecular Life Sciences; Sep2023, Vol. 80 Issue 9, p1-21, 21p
Publication Year :
2023

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. [ABSTRACT FROM AUTHOR]

Details

Language :
English
ISSN :
1420682X
Volume :
80
Issue :
9
Database :
Complementary Index
Journal :
Cellular & Molecular Life Sciences
Publication Type :
Academic Journal
Accession number :
169974895
Full Text :
https://doi.org/10.1007/s00018-023-04878-6