Regulation of ploidy and senescence by the AMPK-related kinase NUAK1
Language: 
English
Abstract: 

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.

Author(s): 
Humbert, Nicolas
Navaratnam, Naveenan
Augert, Arnaud
Da Costa, Marco
Martien, SÈbastien
Wang, Jing
Martinez, Dolores
Abbadie, Corinne
Carling, David
de Launoit, Yvan
Gil, Jesus
Bernard, David
Item Type: 
Journal Article
Publication Title: 
The EMBO journal
Journal Abbreviation: 
EMBO J.
Publication Date: 
1/20/2010
Publication Year: 
2010
Pages: 
376-386
Volume: 
29
Issue: 
2
ISSN: 
1460-2075
DOI: 
10.1038/emboj.2009.342
Library Catalog: 
NCBI Published Medical (?)
Extra: 
PMID: 19927127 PMCID: PMC2824453

Turabian/Chicago Citation

Nicolas Humbert, Naveenan Navaratnam, Arnaud Augert, Marco Da Costa, SÈbastien Martien, Jing Wang, Dolores Martinez, Corinne Abbadie, David Carling, Yvan de Launoit, Jesus Gil and David Bernard. 1/20/2010. "Regulation of ploidy and senescence by the AMPK-related kinase NUAK1." The EMBO journal 29: 2: 376-386. 10.1038/emboj.2009.342.

Wikipedia Citation

<ref> {{Cite journal | doi = 10.1038/emboj.2009.342 | issn = 1460-2075 | volume = 29 | pages = 376-386 | last = Humbert | first = Nicolas | coauthors = Navaratnam, Naveenan, Augert, Arnaud, Da Costa, Marco, Martien, SÈbastien, Wang, Jing, Martinez, Dolores, Abbadie, Corinne, Carling, David, de Launoit, Yvan, Gil, Jesus, Bernard, David | title = Regulation of ploidy and senescence by the AMPK-related kinase NUAK1 | journal = The EMBO journal | date = 1/20/2010 | pmid = | pmc = }} </ref>