2026-07-21T09:04:27Zhttps://repisalud.isciii.es/rest/oai/requestoai:repisalud.isciii.es:20.500.12105/174122024-11-29T23:02:58Zcom_20.500.12105_2173com_20.500.12105_2051col_20.500.12105_19597
Repisalud
author
Humbert, Nicolas
author
Navaratnam, Naveenan
author
Augert, Arnaud
author
Da Costa, Marco
author
Martien, Sébastien
author
Wang, Jing
author
Martinez Garcia, Maria Dolores
author
Abbadie, Corinne
author
Carling, David
author
de Launoit, Yvan
author
Gil, Jesús
author
Bernard, David
funder
RTRS Fondation Synergie Lyon Cancer
funder
Medical Research Council
2024-02-01T12:26:29Z
2024-02-01T12:26:29Z
2010-01-20
EMBO J . 2010 ;29(2):376-86.
10.1038/emboj.2009.342
1460-2075
The EMBO journal
19927127
http://hdl.handle.net/20.500.12105/17412
Senescence is an irreversible cell-cycle arrest that is elicited by a wide range of factors, including replicative exhaustion. Emerging evidences suggest that cellular senescence contributes to ageing and acts as a tumour suppressor mechanism. To identify novel genes regulating senescence, we performed a loss-of-function screen on normal human diploid fibroblasts. We show that downregulation of the AMPK-related protein kinase 5 (ARK5 or NUAK1) results in extension of the cellular replicative lifespan. Interestingly, the levels of NUAK1 are upregulated during senescence whereas its ectopic expression triggers a premature senescence. Cells that constitutively express NUAK1 suffer gross aneuploidies and show diminished expression of the genomic stability regulator LATS1, whereas depletion of NUAK1 with shRNA exerts opposite effects. Interestingly, a dominant-negative form of LATS1 phenocopies NUAK1 effects. Moreover, we show that NUAK1 phosphorylates LATS1 at S464 and this has a role in controlling its stability. In summary, our work highlights a novel role for NUAK1 in the control of cellular senescence and cellular ploidy.
eng
Regulation of ploidy and senescence by the AMPK-related kinase NUAK1.
journal article
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