Regulation of ploidy and senescence by the AMPK-related kinase NUAK1

Nicolas Humbert, Naveenan Navaratnam, Arnaud Augert, Marco Da Costa, Sébastien Martien, Jing Wang, Dolores Martinez, Corinne Abbadie, David Carling, Yvan De Launoit, Jesus Gil, David Bernard

Research output: Contribution to journalArticlepeer-review

77 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)376-386
Number of pages11
JournalEMBO Journal
Issue number2
StatePublished - Jan 2010


  • LATS1
  • NUAK1
  • Senescence

ASJC Scopus subject areas

  • Neuroscience(all)
  • Molecular Biology
  • Biochemistry, Genetics and Molecular Biology(all)
  • Immunology and Microbiology(all)


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