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Werner syndrome protein limits MYC-induced cellular senescence - Supplementary Materials Only

Grandori, C and Wu, KJ and Fernandez, P and Ngouenet, C and Grim, J and Clurman, BE and Moser, MJ and Oshima, J and Russell, DW and Swisshelm, K and Frank, S and Amati, B and Dalla-Favera, R and Monnat, RJ Jr. (2003) Werner syndrome protein limits MYC-induced cellular senescence - Supplementary Materials Only. Genes & Development, 17 (13). pp. 1569-1574. ISSN 0890-9369

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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.

Item Type: Article
Additional Information: For further information contact Carla Grandori at:
DOI: 10.1101/gad.1100303
PubMed ID: 12842909
Depositing User: Library Staff
Date Deposited: 24 Oct 2011 19:35
Last Modified: 14 Feb 2012 14:44

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