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

Research output: Contribution to journalArticle

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.

Original languageEnglish
Pages (from-to)1569-1574
Number of pages6
JournalGenes and Development
Volume17
Issue number13
DOIs
Publication statusPublished - Jul 1 2003

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Keywords

  • Myc
  • Senescence
  • Transcription
  • Werner gene

ASJC Scopus subject areas

  • Genetics
  • Developmental Biology

Cite this

Grandori, C., Wu, K. J., Fernandez, P., Ngouenet, C., Grim, J., Clurman, B. E., Moser, M. J., Oshima, J., Russell, D. W., Swisshelm, K., Frank, S., Amati, B., Dalla-Favera, R., & Monnat, R. J. (2003). Werner syndrome protein limits MYC-induced cellular senescence. Genes and Development, 17(13), 1569-1574. https://doi.org/10.1101/gad.1100303