AMBRA1 phosphorylation by CDK1 and PLK1 regulates mitotic spindle orientation

被引：4

作者：

Faienza, Fiorella ^{[1
,2
]}

Polverino, Federica ^{[3
]}

Rajendraprasad, Girish ^{[4
]}

Milletti, Giacomo ^{[5
,6
]}

Hu, Zehan ^{[7
]}

Colella, Barbara ^{[8
]}

Gargano, Deborah ^{[8
]}

Strappazzon, Flavie ^{[9
,10
]}

Rizza, Salvatore ^{[11
]}

Vistesen, Mette Vixo ^{[1
]}

Luo, Yonglun ^{[12
,13
,14
]}

Antonioli, Manuela ^{[2
,15
]}

Cianfanelli, Valentina ^{[5
,16
,17
]}

Ferraina, Caterina ^{[5
]}

Fimia, Gian Maria ^{[15
,18
]}

Filomeni, Giuseppe ^{[2
,11
,19
]}

De Zio, Daniela ^{[20
,21
]}

Dengjel, Joern ^{[7
]}

Barisic, Marin ^{[4
,22
]}

Guarguaglini, Giulia ^{[3
]}

Di Bartolomeo, Sabrina ^{[8
,23
]}

Cecconi, Francesco ^{[1
,24
]}

机构：

[1] Danish Canc Inst, Ctr Autophagy Recycling & Dis CARD, Cell Stress & Survival Grp, Copenhagen, Denmark

[2] Univ Roma Tor Vergata, Dept Biol, Rome, Italy

[3] CNR Natl Res Council, Inst Mol Biol & Pathol, Rome, Italy

[4] Danish Canc Inst, Cell Div & Cytoskeleton, Copenhagen, Denmark

[5] IRCCS, Bambino Gesu Childrens Hosp, Dept Pediat Hematooncol & Cell & Gene Therapy, Rome, Italy

[6] Danish Canc Inst, DNA Replicat & Canc Grp, DK-2100 Copenhagen, Denmark

[7] Univ Fribourg, Dept Biol, Fribourg, Switzerland

[8] Univ Molise, Dept Biosci & Terr, Pesche, Italy

[9] IRCCS Fdn Santa Lucia, Rome, Italy

[10] Univ Lyon 1, Univ Lyon, Physiopathol & Genet Neurone & Muscle, Inst NeuroMyogene,UMR5261,U1315,CNRS,INSERM, F-69008 Lyon, France

[11] Danish Canc Inst, Redox Biol Grp, Copenhagen, Denmark

[12] BGI Res, Lars Bolund Inst Regenerat Med, Shenzhen, Peoples R China

[13] BGI Res, Qingdao Europe Adv Inst Life Sci, Shenzhen, Peoples R China

[14] Aarhus Univ, Dept Biomed, Aarhus, Denmark

[15] IRCSS L Spallanzani, Natl Inst Infect Dis, Rome, Italy

[16] Univ ROMA TRE, Dept Sci, I-00146 Rome, Italy

[17] Fdn Policlin Univ A Gemelli IRCCS, Dept Woman & Child Hlth & Publ Hlth, Gynecol Oncol Unit, Rome, Italy

[18] Sapienza Univ Rome, Dept Mol Med, Rome, Italy

[19] Univ Copenhagen, Ctr Hlth Aging, Copenhagen, Denmark

[20] Danish Canc Inst, Melanoma Res Team, Copenhagen, Denmark

[21] Univ Copenhagen, Dept Drug Design & Pharmacol, Copenhagen, Denmark

[22] Univ Copenhagen, Fac Hlth Sci, Dept Cellular & Mol Med, Copenhagen, Denmark

[23] Univ Cattolica Sacro Cuore, Rome, Italy

[24] Fdn Policlin Univ Agostino Gemelli IRCCS, Rome, Italy

来源：

CELLULAR AND MOLECULAR LIFE SCIENCES | 2023年 / 80卷 / 09期

关键词：

Phosphorylation; Cell cycle; Mitotic kinases; Mitotic spindle; NUMA1; CORTICAL DYNEIN; NUMA PHOSPHORYLATION; INHIBITS AUTOPHAGY; BH3-LIKE PROTEIN; PROGRESSION; CELLS; DEGRADATION; CHROMOSOME; WASH;

D O I：

10.1007/s00018-023-04878-6

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

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.

引用

页数：21

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