Werner syndrome protein limits MYC-induced cellular senescence

Carla Grandori*, Kou Juey Wu, Paula Fernandez, Celine Ngouenet, Jonathan Grim, Bruce E. Clurman, Michael J. Moser, Junko Oshima, David W. Russell, Karen Swisshelm, Scott Frank, Bruno Amati, Riccardo Dalla-Favera, Raymond J. Monnat

*Corresponding author for this work

Research output: Contribution to journalJournal Article peer-review

158 Scopus citations


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.

Original languageEnglish
Pages (from-to)1569-1574
Number of pages6
JournalGenes and Development
Issue number13
StatePublished - 01 07 2003
Externally publishedYes


  • Myc
  • Senescence
  • Transcription
  • Werner gene


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