p53-mediated apoptosis is attenuated in Werner syndrome cells.
The WRN DNA helicase is a member of the DExH-containing DNA helicase superfamily that includes XPB, XPD, and BLM. Mutations in WRN are found in patients with the premature aging and cancer susceptibility syndrome known as Werner syndrome (WS). p53 binds to the WRN protein in vivo and in vitro through its carboxyl terminus. WS fibroblasts have an attenuated p53- mediated apoptotic response, and this deficiency can be rescued by expression of wild-type WRN. These data support the hypothesis that p53 can induce apoptosis through the modulation of specific DExH-containing DNA helicases and may have implications for the cancer predisposition observed in WS patients.
Spillare
E A
EA
Laboratory of Human Carcinogenesis, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892-4255, USA.
Robles
A I
AI
Wang
X W
XW
Shen
J C
JC
Yu
C E
CE
Schellenberg
G D
GD
Harris
C C
CC
D000818:Animals; D017209:Apoptosis; D004265:DNA Helicases / Q000235:genetics / Q000378:metabolism*; D005090:Exodeoxyribonucleases; D005347:Fibroblasts / Q000166:cytology / Q000378:metabolism; D006801:Humans; D051379:Mice; D053484:RecQ Helicases; D014407:Tumor Cells, Cultured; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism*; D014898:Werner Syndrome / Q000473:pathology*; D000071657:Werner Syndrome Helicase
D016159:Tumor Suppressor Protein p53; D005090:Exodeoxyribonucleases; D004265:DNA Helicases; D053484:RecQ Helicases; C098785:WRN protein, human; D000071657:Werner Syndrome Helicase