Werner syndrome protein limits MYC-induced cellular senescence
- 1 July 2003
- journal article
- Published by Cold Spring Harbor Laboratory in Genes & Development
- Vol. 17 (13) , 1569-1574
- https://doi.org/10.1101/gad.1100303
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 inWRNlead 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 byhTERTexpression. We propose thatWRNup-regulation by MYC may promote MYC-driven tumorigenesis by preventing cellular senescence.Keywords
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