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Genes Dev. 2003 Jul 1;17(13):1569-74.

Werner syndrome protein limits MYC-induced cellular senescence.

Author information

1
Basic Sciences, Human Biology and Clinical Divisions, Fred Hutchinson Cancer Research Center, Seattle, Washington 98109, USA. cgrandor@fhcrc.org

Abstract

The MYC oncoprotein is a transcription factor that coordinates cell growth and division. MYC overexpression exacerbates genomic instability and sensitizes cells to apoptotic stimuli. Here we demonstrate that MYC directly stimulates transcription of the human Werner syndrome gene, WRN, which encodes a conserved RecQ helicase. Loss-of-function mutations in WRN lead to genomic instability, an elevated cancer risk, and premature cellular senescence. The overexpression of MYC in WRN syndrome fibroblasts or after WRN depletion from control fibroblasts led to rapid cellular senescence that could not be suppressed by hTERT expression. We propose that WRN up-regulation by MYC may promote MYC-driven tumorigenesis by preventing cellular senescence.

PMID:
12842909
PMCID:
PMC196129
DOI:
10.1101/gad.1100303
[Indexed for MEDLINE]
Free PMC Article

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