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

doi:10.1101/gad.1100303

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 journal › Journal Article › peer-review

161 Scopus citations

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 language	English
Pages (from-to)	1569-1574
Number of pages	6
Journal	Genes and Development
Volume	17
Issue number	13
DOIs	https://doi.org/10.1101/gad.1100303
State	Published - 01 07 2003
Externally published	Yes

Keywords

Myc
Senescence
Transcription
Werner gene

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1101/gad.1100303

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title = "Werner syndrome protein limits MYC-induced cellular senescence",

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.",

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T1 - Werner syndrome protein limits MYC-induced cellular senescence

AU - Grandori, Carla

AU - Wu, Kou Juey

AU - Fernandez, Paula

AU - Ngouenet, Celine

AU - Grim, Jonathan

AU - Clurman, Bruce E.

AU - Moser, Michael J.

AU - Oshima, Junko

AU - Russell, David W.

AU - Swisshelm, Karen

AU - Frank, Scott

AU - Amati, Bruno

AU - Dalla-Favera, Riccardo

AU - Monnat, Raymond J.

PY - 2003/7/1

Y1 - 2003/7/1

N2 - 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.

AB - 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.

KW - Myc

KW - Senescence

KW - Transcription

KW - Werner gene

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DO - 10.1101/gad.1100303

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SP - 1569

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JO - Genes and Development

JF - Genes and Development

IS - 13

ER -

Werner syndrome protein limits MYC-induced cellular senescence

Abstract

Keywords

UN SDGs

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