Functional link between Myc and the Werner gene in tumorigenesis.
We have recently reported a connection between the expression of the Werner syndrome gene (WRN), whose loss of function has been implicated in a human progeroid syndrome (WS), and the Myc oncoprotein. Myc overexpression directly elevates trancription of the WRN gene, whose presence is required to avoid senescence during Myc proliferative stimuli. Here we discuss several hypotheses to explain why WRN might be required to support oncogenic proliferation in light of the known function of WRNprotein and Myc in genomic instability and transcriptional modulation. In addition, we address the apparent paradox of why patients with WS, lacking WRN function, have increased incidence of certain cancers.
Grandori
Carla
C
Division of Human Biology, Fred Hutchinson Cancer Research Center, Seattle, Washington 98109, USA. cgrandor@fhcrc.org
Robinson
Kristin L
KL
Galloway
Denise A
DA
Swisshelm
Karen
K
D000818:Animals; D002455:Cell Division / Q000502:physiology; D002471:Cell Transformation, Neoplastic / Q000235:genetics*; D016922:Cellular Senescence / Q000235:genetics / Q000502:physiology*; D004265:DNA Helicases / Q000235:genetics / Q000378:metabolism*; D004268:DNA-Binding Proteins; D005090:Exodeoxyribonucleases; D016259:Genes, myc / Q000235:genetics / Q000502:physiology*; D006801:Humans; D008223:Lymphoma / Q000150:complications / Q000235:genetics; D009154:Mutation; D011401:Promoter Regions, Genetic / Q000235:genetics; D034741:RNA, Small Interfering / Q000378:metabolism; D053484:RecQ Helicases; D019098:Telomerase / Q000378:metabolism; D014407:Tumor Cells, Cultured; D014898:Werner Syndrome / Q000150:complications / Q000235:genetics*; D000071657:Werner Syndrome Helicase
D004268:DNA-Binding Proteins; D034741:RNA, Small Interfering; D019098:Telomerase; D005090:Exodeoxyribonucleases; D004265:DNA Helicases; D053484:RecQ Helicases; C098785:WRN protein, human; D000071657:Werner Syndrome Helicase